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Skeletal dysplasia v4.55 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti 308300; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency 300301 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Skeletal dysplasia v4.54 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from RAPILINO syndrome 266280; Rothmund-Thomson syndrome 268400; Baller-Gerold syndrome 218600 to Baller-Gerold syndrome, OMIM:218600; RAPADILINO syndrome, OMIM:266280; Rothmund-Thomson syndrome, type 2, OMIM:268400
Skeletal dysplasia v4.53 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900; Schimke immunoosseous dysplasia 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Skeletal dysplasia v4.52 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from Craniofrontonasal dysplasia 304110 to Craniofrontonasal dysplasia, OMIM:304110
Skeletal dysplasia v4.51 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short rib polydactyly syndrome (SRPS) type 3 with or without polydactyly, 613091; Short rib polydactyly syndrome (SRPS) type 1/3 (Saldino-Noonan/Verma-Naumoff); Asphyxiating thoracic dystrophy 3, 613091Short rib-polydactyly syndrome, type III, 263510Short rib-polydactyly syndrome, type IIB, 615087 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Skeletal dysplasia v4.50 TP53 Sarah Leigh Classified gene: TP53 as Red List (low evidence)
Skeletal dysplasia v4.50 TP53 Sarah Leigh Gene: tp53 has been classified as Red List (Low Evidence).
Skeletal dysplasia v4.49 TP53 Sarah Leigh edited their review of gene: TP53: Added comment: This gene is rated as red, because the variants are somatic, occurring in the tumour.; Changed rating: RED
Skeletal dysplasia v4.49 TP53 Sarah Leigh changed review comment from: PMID: 33147331 reports inactivating somatic TP53 variants in dedifferentiated components of dedifferentiated chondrosarcoma. Due to the distribution of TP53 variants in the tumours, the authors of PMID: 33147331, conclude that these variants occur late in tumorigenesis, giving rise to the dedifferentiated component in DDCS.
This gene is rated as red, because the variants are somatic, occurring in the tumour.; to: PMID: 33147331 reports inactivating somatic TP53 variants in dedifferentiated components of dedifferentiated chondrosarcoma. Due to the distribution of TP53 variants in the tumours, the authors of PMID: 33147331, conclude that these variants occur late in tumorigenesis, giving rise to the dedifferentiated component in DDCS.
Skeletal dysplasia v4.49 TP53 Sarah Leigh changed review comment from: PMID: 33147331 reports inactivating TP53 variants in dedifferentiated components of dedifferentiated chondrosarcoma. Due to the distribution of TP53 variants in the tumours, the authors of PMID: 33147331, conclude that these variants occur late in
tumorigenesis, giving rise to the dedifferentiated component in DDCS.; to: PMID: 33147331 reports inactivating somatic TP53 variants in dedifferentiated components of dedifferentiated chondrosarcoma. Due to the distribution of TP53 variants in the tumours, the authors of PMID: 33147331, conclude that these variants occur late in tumorigenesis, giving rise to the dedifferentiated component in DDCS.
This gene is rated as red, because the variants are somatic, occurring in the tumour.
Skeletal dysplasia v4.49 IDH2 Sarah Leigh Deleted their comment
Skeletal dysplasia v4.49 IDH2 Sarah Leigh Classified gene: IDH2 as Red List (low evidence)
Skeletal dysplasia v4.49 IDH2 Sarah Leigh Gene: idh2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v4.48 IDH2 Sarah Leigh changed review comment from: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.
This gene is rated as amber, because the variants are somatic, occurring in the tumour.; to: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.
This gene is rated as red, because the variants are somatic, occurring in the tumour.
Skeletal dysplasia v4.48 MGP Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As there is sufficient evidence available (two unrelated cased and functional studies) for the association of monoallelic MGP variants with spondyloepiphyseal dysplasia, the MOI should be updated from 'BIALLELIC, autosomal or pseudoautosomal' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS review.
Skeletal dysplasia v4.48 MGP Achchuthan Shanmugasundram Mode of inheritance for gene: MGP was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.47 MGP Achchuthan Shanmugasundram Phenotypes for gene: MGP were changed from Keutel syndrome 245150; Keutel syndrome 245150 to Keutel syndrome, OMIM:245150; spondyloepiphyseal dysplasia, MONDO:0016761
Skeletal dysplasia v4.46 MGP Achchuthan Shanmugasundram Publications for gene: MGP were set to
Skeletal dysplasia v4.45 MGP Achchuthan Shanmugasundram Tag Q1_24_MOI tag was added to gene: MGP.
Skeletal dysplasia v4.45 MGP Achchuthan Shanmugasundram changed review comment from: PMID:37923733 reported four individuals from two unrelated families with two different heterozygous MGP variants affecting Cys 19 residue (family 1: p.Cys19Phe; family 2: p.Cys19Tyr) and with previously undescribed spondyloepiphyseal dysplasia characterized by short stature with a short trunk, diffuse platyspondyly, midface retrusion, progressive epiphyseal anomalies and brachytelephalangism. In addition, functional evidence from heterozygous ‘knock-in’ mice expressing Cys19Phe MGP recapitulate most of the skeletal anomalies observed in the affected individuals.; to: PMID:37923733 reported four individuals from two unrelated families with two different heterozygous MGP variants affecting Cys 19 residue (family 1: p.Cys19Phe; family 2: p.Cys19Tyr) and with previously undescribed spondyloepiphyseal dysplasia characterized by short stature with a short trunk, diffuse platyspondyly, midface retrusion, progressive epiphyseal anomalies and brachytelephalangism. In addition, functional evidence from heterozygous ‘knock-in’ mice expressing Cys19Phe MGP recapitulate most of the skeletal anomalies observed in the affected individuals.

Although phenotype caused by biallelic MGP variants are already reported in both OMIM (MIM #245150) and Gene2Phenotype, phenotype caused by monoallelic variants are not yet reported in either resources.
Skeletal dysplasia v4.45 MGP Achchuthan Shanmugasundram edited their review of gene: MGP: Changed phenotypes to: Keutel syndrome, OMIM:245150, spondyloepiphyseal dysplasia, MONDO:0016761
Skeletal dysplasia v4.45 MGP Achchuthan Shanmugasundram reviewed gene: MGP: Rating: GREEN; Mode of pathogenicity: None; Publications: 37923733; Phenotypes: spondyloepiphyseal dysplasia, MONDO:0016761; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v4.45 TP53 Sarah Leigh edited their review of gene: TP53: Added comment: PMID: 33147331 reports inactivating TP53 variants in dedifferentiated components of dedifferentiated chondrosarcoma. Due to the distribution of TP53 variants in the tumours, the authors of PMID: 33147331, conclude that these variants occur late in
tumorigenesis, giving rise to the dedifferentiated component in DDCS.; Changed rating: AMBER
Skeletal dysplasia v4.45 TP53 Sarah Leigh Added comment: Comment on mode of inheritance: TP53 variants associated with chondrosarcomas are somatic, occurring in the tumour material.
Skeletal dysplasia v4.45 TP53 Sarah Leigh Mode of inheritance for gene: TP53 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Skeletal dysplasia v4.44 TP53 Sarah Leigh Tag somatic tag was added to gene: TP53.
Skeletal dysplasia v4.44 IDH2 Sarah Leigh Added comment: Comment on mode of inheritance: IDH2 variants associated with chondrosarcomas are somatic, occurring in the tumour material.
Skeletal dysplasia v4.44 IDH2 Sarah Leigh Mode of inheritance for gene: IDH2 was changed from Other to Other
Skeletal dysplasia v4.44 IDH2 Sarah Leigh Added comment: Comment on mode of inheritance: IDH2 variants associated with chondrosarcomas are somatic, occurring in the tumour material.
Skeletal dysplasia v4.44 IDH2 Sarah Leigh Mode of inheritance for gene: IDH2 was changed from Unknown to Other
Skeletal dysplasia v4.43 IDH2 Sarah Leigh changed review comment from: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.; to: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.
This gene is rated as amber, because the variants are somatic, occurring in the tumour.
Skeletal dysplasia v4.43 IDH2 Sarah Leigh edited their review of gene: IDH2: Changed rating: AMBER
Skeletal dysplasia v4.43 IDH2 Sarah Leigh Tag Q1_24_promote_green was removed from gene: IDH2.
Tag Q1_24_NHS_review was removed from gene: IDH2.
Tag somatic tag was added to gene: IDH2.
Skeletal dysplasia v4.43 TP53 Sarah Leigh Publications for gene: TP53 were set to PMID: 33147331
Skeletal dysplasia v4.42 TP53 Sarah Leigh Classified gene: TP53 as Amber List (moderate evidence)
Skeletal dysplasia v4.42 TP53 Sarah Leigh Gene: tp53 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.41 IDH2 Sarah Leigh Classified gene: IDH2 as Amber List (moderate evidence)
Skeletal dysplasia v4.41 IDH2 Sarah Leigh Gene: idh2 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.40 IDH2 Sarah Leigh Phenotypes for gene: IDH2 were changed from Maffucci syndrome 614569; Enchondromatosis (Ollier) and Enchondromatosis with hermangiomata (Maffucci) 166000, metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (614875); Ollier disease/ Dyschondroplasia 166000; D-2-hydroxyglutaric aciduria 2 613657 to D-2-hydroxyglutaric aciduria 2, OMIM:613657; d-2-hydroxyglutaric aciduria 2, MONDO:0013345
Skeletal dysplasia v4.39 IDH2 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: IDH2.
Tag Q1_24_NHS_review tag was added to gene: IDH2.
Skeletal dysplasia v4.39 IDH2 Sarah Leigh edited their review of gene: IDH2: Added comment: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.; Changed rating: GREEN
Skeletal dysplasia v4.39 IDH2 Sarah Leigh Publications for gene: IDH2 were set to 24049096; 22057234; 22057236
Skeletal dysplasia v4.38 FBXW11 Achchuthan Shanmugasundram Tag Q4_21_NHS_review was removed from gene: FBXW11.
Tag Q4_23_NHS_review tag was added to gene: FBXW11.
Skeletal dysplasia v4.38 NEPRO Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: NEPRO.
Skeletal dysplasia v4.38 NEPRO Achchuthan Shanmugasundram Classified gene: NEPRO as Amber List (moderate evidence)
Skeletal dysplasia v4.38 NEPRO Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases reported with three different homozygous variants in NEPRO gene. Three unrelated cases were of Arabic/ partial Arabic descent, while the fourth case from India. The evidence available is sufficient enough to promote the rating to green in the next GMS review.
Skeletal dysplasia v4.38 NEPRO Achchuthan Shanmugasundram Gene: nepro has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.37 NEPRO Achchuthan Shanmugasundram Phenotypes for gene: NEPRO were changed from Anauxetic dysplasia 3, MIM618853 to Anauxetic dysplasia 3, OMIM:618853
Skeletal dysplasia v4.36 NEPRO Achchuthan Shanmugasundram Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
Skeletal dysplasia v4.35 NEPRO Achchuthan Shanmugasundram changed review comment from: PMID:26633546 reported a sister and brother among 31 Saudi Arabian families studied with skeletal dysplasia and homozygous missense variant in NEPRO gene (p.Arg49Cys).

PMID:29620724 reported the same homozygous NEPRO variant (p.Arg49Cys) in two brothers of Arab descent with skeletal dysplasia. The disorder is identical to phenotypes reported in PMID:26633546 and haplotype analysis confirmed the founder nature of the variant.

PMID:31250547 reported a 13-year-old Indian girl with a different homozygous missense variant (p.Leu145Phe) and with severe short stature and skeletal dysplasia with sparse scalp hair and skin and joint laxity. Her second-cousin parents were heterozygous for the same variant.

This gene has been associated with relevant phenotypes in OMIM (MIM #618853), but not in Gene2Phenotype.; to: PMID:26633546 reported a sister and brother among 31 Saudi Arabian families studied with skeletal dysplasia and homozygous missense variant in NEPRO gene (p.Arg49Cys).

PMID:29620724 reported the same homozygous NEPRO variant (p.Arg49Cys) in two brothers of Arab descent with skeletal dysplasia. The disorder is identical to phenotypes reported in PMID:26633546 and haplotype analysis confirmed the founder nature of the variant.

PMID:31250547 reported a 13-year-old Indian girl with a different homozygous missense variant (p.Leu145Phe) and with severe short stature and skeletal dysplasia with sparse scalp hair and skin and joint laxity. Her second-cousin parents were heterozygous for the same variant.

PMID:37294112 reported a 7-year-old girl from an Arabic-speaking community in Eastern Africa with Anauxetic dysplasia 3 and another homozygous NEPRO variant (p.Arg94Cys). She was born to consanguineous parents, who reported that their shared ancestor was of Arab descent. This patient presented with clinically relevant features not previously described in ANXD3: atlantoaxial subluxation, extensive dental anomalies, and a sagittal suture craniosynostosis resulting in scaphocephaly.

This gene has been associated with relevant phenotypes in OMIM (MIM #618853), but not in Gene2Phenotype.
Skeletal dysplasia v4.35 NEPRO Achchuthan Shanmugasundram edited their review of gene: NEPRO: Changed rating: GREEN; Changed publications to: 26633546, 29620724, 31250547, 37294112
Skeletal dysplasia v4.35 NEPRO Achchuthan Shanmugasundram reviewed gene: NEPRO: Rating: AMBER; Mode of pathogenicity: None; Publications: 26633546, 29620724, 31250547; Phenotypes: Anauxetic dysplasia 3, OMIM:618853; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.35 IDH2 Adrienne Flanagan reviewed gene: IDH2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 36042521; Phenotypes: Chondrosarcoma Conventional Central; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v4.35 TP53 Adrienne Flanagan gene: TP53 was added
gene: TP53 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TP53 were set to PMID: 33147331
Phenotypes for gene: TP53 were set to Central conventional chondrosrcoma
Review for gene: TP53 was set to GREEN
Added comment: Inactivating mutations in TP53 are common in dedifferentiated chondrosarcoma (DDCS) and, in a subset of cases, the TP53 mutation is restricted to the dedifferentiated nonchondrogenic component (8/11, 73% of the cases tested). Half of the tumours where the conventional chondrogenic component was paired with the high-grade non-chondrogenic component showed TP53 mutation in the chondrogenic area (3/6, 50%). These findings imply that TP53 alterations occur late in tumorigenesis, potentially with a TP53-mutant subclone that progresses to the dedifferentiated component in DDCS. Identification of TP53 mutation in an otherwise low-grade central chondrosarcoma may indicate the tumor is at increased risk of dedifferentiation.
Genetic testing for TP53 along with IDH1, IDH2 and TERT promoter mutations in central conventional chondrosarcoma could be useful in patient stratification.
Sources: Literature
Skeletal dysplasia v4.35 FBXW11 Sarah Leigh Phenotypes for gene: FBXW11 were changed from Global developmental delay; Intellectual disability; Abnormality of the eye; Abnormality of the head; Abnormality of digit; Neurodevelopmental, jaw, eye, and digital syndrome MIM#618914 to Neurodevelopmental, jaw, eye, and digital syndrome, OMIM:618914; neurodevelopmental, jaw, eye, and digital syndrome, MONDO:0030057
Skeletal dysplasia v4.34 FBXW11 Sarah Leigh Tag Q4_21_NHS_review tag was added to gene: FBXW11.
Tag Q4_23_promote_green tag was added to gene: FBXW11.
Skeletal dysplasia v4.34 FBXW11 Sarah Leigh reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v4.34 FBXW11 Sarah Leigh Classified gene: FBXW11 as Amber List (moderate evidence)
Skeletal dysplasia v4.34 FBXW11 Sarah Leigh Gene: fbxw11 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.33 FBXW11 Sarah Leigh Entity copied from Intellectual disability - microarray and sequencing v5.369
Skeletal dysplasia v4.33 FBXW11 Sarah Leigh gene: FBXW11 was added
gene: FBXW11 was added to Skeletal dysplasia. Sources: Literature,Expert Review Green
Mode of inheritance for gene: FBXW11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FBXW11 were set to 31402090
Phenotypes for gene: FBXW11 were set to Global developmental delay; Intellectual disability; Abnormality of the eye; Abnormality of the head; Abnormality of digit; Neurodevelopmental, jaw, eye, and digital syndrome MIM#618914
Penetrance for gene: FBXW11 were set to unknown
Skeletal dysplasia v4.32 UBA2 Eleanor Williams Tag Q4_23_promote_green tag was added to gene: UBA2.
Tag Q4_23_NHS_review tag was added to gene: UBA2.
Skeletal dysplasia v4.32 UBA2 Eleanor Williams commented on gene: UBA2: As reviewer notes there are now additional cases reported with variants in UBA2 and skeletal defects including:

PMID: 34040189 - Schnur et al 2021 - report 16 individuals from 7 families who have variable phenotypes including Aplasia cutis congenita and skeletal defects. Ectrodyctly is present in some individuals from 4/7 families and other skeletal phenotypes such as hip abnormalities, plagiocephaly, Wormian bones, syndactyly, kyphoscoliosis, Variants were heterozygous rare variants not found in GnomAD and consist of frameshift, nonsense and missense variants.
Skeletal dysplasia v4.32 PSMC3 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: PSMC3.
Skeletal dysplasia v4.32 PSMC3 Achchuthan Shanmugasundram Classified gene: PSMC3 as Amber List (moderate evidence)
Skeletal dysplasia v4.32 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of monoallelic PSMC3 variants with skeletal malformations and hence this gene can be promoted to green rating in the next GMS review.
Skeletal dysplasia v4.32 PSMC3 Achchuthan Shanmugasundram Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.31 PSMC3 Achchuthan Shanmugasundram changed review comment from: 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Skeletal malformations were observed in 11/15 (73%) cases (scoliosis, acetabular dysplasia, brachymetatarsy)
Sources: Literature; to: 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Skeletal malformations were observed in 11/15 (73%) cases (scoliosis, acetabular dysplasia, brachymetatarsy).

Monoallelic variants in PSMC3 are not yet associated with any relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Skeletal dysplasia v4.31 PSMC3 Achchuthan Shanmugasundram gene: PSMC3 was added
gene: PSMC3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC3 were set to 37256937
Phenotypes for gene: PSMC3 were set to neurodevelopmental disorder, MONDO:0700092; scoliosis, MONDO:0005392; Acetabular dysplasia, HP:0008807; brachymetatarsy
Review for gene: PSMC3 was set to GREEN
Added comment: 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Skeletal malformations were observed in 11/15 (73%) cases (scoliosis, acetabular dysplasia, brachymetatarsy)
Sources: Literature
Skeletal dysplasia v4.30 FAM111A Sarah Leigh Added comment: Comment on mode of inheritance: PMID: 34382758 reports an autosomal recessive case of Kenny-Caffey Syndrome Type 2. The proband had inherited FAM111A variants from his healthy parents (paternal heterozygous missense
variant c.976T>A (p.L326I) and maternal heterozygous
in-frame deletion variant c.1714_1716del (p.Ile572del,
rs779963813)).
Skeletal dysplasia v4.30 FAM111A Sarah Leigh Mode of inheritance for gene: FAM111A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v4.29 FAM111A Sarah Leigh Publications for gene: FAM111A were set to
Skeletal dysplasia v4.25 ERI1 Achchuthan Shanmugasundram Classified gene: ERI1 as Amber List (moderate evidence)
Skeletal dysplasia v4.25 ERI1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for promotion of this gene to green rating in the next GMS review.
Skeletal dysplasia v4.25 ERI1 Achchuthan Shanmugasundram Gene: eri1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.24 ERI1 Achchuthan Shanmugasundram Tag Q4_23_NHS_review tag was added to gene: ERI1.
Skeletal dysplasia v4.24 ERI1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Tracy Lester, four patients from three different families were identified with compound heterozygous missense variants in ERI1 gene and were reported with spondyloepimetaphyseal dysplasia. In addition, another unrelated patient with a missense and a null variant was reported with spondyloepimetaphyseal dysplasia, and delayed motor milestones and speech and generalised hypotonia.; to: As reviewed by Tracy Lester, four patients from three different families were identified with compound heterozygous missense variants in ERI1 gene and were reported with spondyloepimetaphyseal dysplasia. In addition, another unrelated patient with a missense and a null variant was reported with spondyloepimetaphyseal dysplasia, and delayed motor milestones and speech and generalised hypotonia (PMID:37352860).


This gene has not yet been associated with relevantly phenotypes either in OMIM or in Gene2Phenotype.
Skeletal dysplasia v4.24 ERI1 Achchuthan Shanmugasundram commented on gene: ERI1: As reviewed by Tracy Lester, four patients from three different families were identified with compound heterozygous missense variants in ERI1 gene and were reported with spondyloepimetaphyseal dysplasia. In addition, another unrelated patient with a missense and a null variant was reported with spondyloepimetaphyseal dysplasia, and delayed motor milestones and speech and generalised hypotonia.
Skeletal dysplasia v4.24 ERI1 Achchuthan Shanmugasundram Phenotypes for gene: ERI1 were changed from spondyloepimetaphyseal dysplasia; digital anomalies to spondyloepimetaphyseal dysplasia, MONDO:0100510
Skeletal dysplasia v4.23 ERI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ERI1.
Skeletal dysplasia v4.23 ERI1 Achchuthan Shanmugasundram reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37352860; Phenotypes: spondyloepimetaphyseal dysplasia, MONDO:0100510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.23 TMEM251 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: TMEM251.
Tag gene-checked tag was added to gene: TMEM251.
Skeletal dysplasia v4.23 TMEM251 Achchuthan Shanmugasundram commented on gene: TMEM251
Skeletal dysplasia v4.23 KIF24 Eleanor Williams Tag gene-checked tag was added to gene: KIF24.
Skeletal dysplasia v4.23 KIF24 Eleanor Williams commented on gene: KIF24: This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:35748595 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tag
Skeletal dysplasia v4.23 AXIN1 Achchuthan Shanmugasundram Classified gene: AXIN1 as Amber List (moderate evidence)
Skeletal dysplasia v4.23 AXIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Skeletal dysplasia v4.23 AXIN1 Achchuthan Shanmugasundram Gene: axin1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.22 AXIN1 Achchuthan Shanmugasundram Phenotypes for gene: AXIN1 were changed from Syndromic disease, (MONDO:0002254), AXIN1-related; skeletal dysplasia to neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, MONDO:0018681
Skeletal dysplasia v4.21 AXIN1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: AXIN1.
Skeletal dysplasia v4.21 AXIN1 Achchuthan Shanmugasundram reviewed gene: AXIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37582359; Phenotypes: neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, MONDO:0018681; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.20 KIF24 Eleanor Williams Tag Q4_22_promote_green was removed from gene: KIF24.
Skeletal dysplasia v4.20 GPX4 Eleanor Williams Tag Q2_23_promote_green was removed from gene: GPX4.
Skeletal dysplasia v4.20 GNAS Eleanor Williams Tag Q4_22_MOI was removed from gene: GNAS.
Skeletal dysplasia v4.20 FGF9 Eleanor Williams Tag Q2_23_promote_green was removed from gene: FGF9.
Skeletal dysplasia v4.20 DDRGK1 Eleanor Williams Tag Q1_23_promote_green was removed from gene: DDRGK1.
Skeletal dysplasia v4.20 KIF24 Eleanor Williams reviewed gene: KIF24: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.20 GPX4 Eleanor Williams edited their review of gene: GPX4: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.20 GNAS Eleanor Williams edited their review of gene: GNAS: Added comment: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v4.20 FGF9 Eleanor Williams edited their review of gene: FGF9: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v4.20 DDRGK1 Eleanor Williams reviewed gene: DDRGK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.19 KIF24 Eleanor Williams Source NHS GMS was added to KIF24.
Source Expert Review Green was added to KIF24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v4.19 GPX4 Eleanor Williams Source Expert Review Green was added to GPX4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v4.19 GNAS Eleanor Williams Mode of inheritance for gene GNAS was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v4.19 FGF9 Eleanor Williams Source Expert Review Green was added to FGF9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v4.19 DDRGK1 Eleanor Williams Source NHS GMS was added to DDRGK1.
Source Expert Review Green was added to DDRGK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v4.18 ERI1 Tracy Lester edited their review of gene: ERI1: Added comment: >3 cases confirmed; Changed rating: GREEN
Skeletal dysplasia v4.18 ERI1 Tracy Lester gene: ERI1 was added
gene: ERI1 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to spondyloepimetaphyseal dysplasia; digital anomalies
Penetrance for gene: ERI1 were set to unknown
Mode of pathogenicity for gene: ERI1 was set to Other
Added comment: In this study, the authors uncovered a phenotypic dichotomy in eight individuals from seven unrelated families with different types of ERI1 variants and highlighted the association of missense variants with spondyloepimetaphyseal dysplasia (SEMD), which is a group of skeletal diseases characterized by anomalies in spine and long tubular bones.In contrast, the affected individuals with bi-allelic null variants showed mild intellectual disability and digital anomalies. The detailed evaluation of the skeletal phenotypes of Eri1 knockout (KO) mice and the in vitro chondrogenesis of affected-individual-derived induced pluripotent stem cells (iPSCs) supported the functional involvement of ERI1 in skeletal development. Analyses using ERI1 KO HeLa cells
and affected-individual-derived cells demonstrated functional conservation of ERI1 with its mouse ortholog in 5.8S rRNA maturation and histone mRNAs decay. The 5.8S
rRNA maturation is involved in ribosome biogenesis, defects of which are known to cause ribosomopathies characterized by skeletal dysplasia.12–15 Our study leads to the findings of an SEMD associated with ribosomopathy and established a framework for understanding the molecular mechanisms underlying the ERI1 phenotypic dichotomy.

Missense variants reported to affect residues 134,150, 155, 298 and 299. All cases with biallelic missense variants had short stature, epiphyseal, spinal and digit anomalies, as well as other variable kidney and cardiac anomalies. One case with a LOF and a missense was reported with these features and intellectual disability/developmental delay. The 3 cases with biallelic LOF variants had ID/DD, digital anomalies without the other (height varied from 8th centile to normal).
Sources: NHS GMS
Skeletal dysplasia v4.18 AXIN1 Zornitza Stark gene: AXIN1 was added
gene: AXIN1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: AXIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AXIN1 were set to 37582359
Phenotypes for gene: AXIN1 were set to Syndromic disease, (MONDO:0002254), AXIN1-related; skeletal dysplasia
Review for gene: AXIN1 was set to GREEN
Added comment: PMID: 37582359
- four families (7 individuals) with three homozygous truncating variants.
- all variant shown to result in reduced protein, though 1/3 would be NMD predicted
- Probands had macrocephaly (4/6), GDD (3/7), hip dysplasia (5/6), cardiac anomalies eg. VSD/ASD (3/7), cranial hyperostosis and vertebral endplate sclerosis
Sources: Literature
Skeletal dysplasia v4.18 TP63 Arina Puzriakova Phenotypes for gene: TP63 were changed from ADULT syndrome, OMIM:103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM:604292; Limb-mammary syndrome, OMIM:603543 to ADULT syndrome, OMIM:103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM:604292; Limb-mammary syndrome, OMIM:603543; Split-hand/foot malformation 4, OMIM:605289
Skeletal dysplasia v4.17 TP63 Arina Puzriakova Phenotypes for gene: TP63 were changed from Rapp-Hodgkin syndrome 129400; Orofacial cleft 8 129400; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 604292; Hay-Wells syndrome 106260; ULT syndrome 103285; Split-hand/foot malformation 4 605289; Limb-mammary syndrome 603543 to ADULT syndrome, OMIM:103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM:604292; Limb-mammary syndrome, OMIM:603543
Skeletal dysplasia v4.16 PKDCC Arina Puzriakova Phenotypes for gene: PKDCC were changed from Rhizomelia; dysmorphism to Rhizomelic limb shortening with dysmorphic features, OMIM:618821
Skeletal dysplasia v4.15 UBA2 Tracy Lester reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v4.15 SETD5 Achchuthan Shanmugasundram Phenotypes for gene: SETD5 were changed from Intellectual developmental disorder, autosomal dominant 23, OMIM:615761; Skeletal dysplasia; intellectual disability; developmental delay; facial dysmorphism to Intellectual developmental disorder, autosomal dominant 23, OMIM:615761; skeletal dysplasia, MONDO:0018230; facial dysmorphism
Skeletal dysplasia v4.14 SETD5 Achchuthan Shanmugasundram edited their review of gene: SETD5: Changed phenotypes to: Intellectual developmental disorder, autosomal dominant 23, OMIM:615761, skeletal dysplasia, MONDO:0018230
Skeletal dysplasia v4.14 SETD5 Achchuthan Shanmugasundram Deleted their comment
Skeletal dysplasia v4.14 SETD5 Achchuthan Shanmugasundram Classified gene: SETD5 as Amber List (moderate evidence)
Skeletal dysplasia v4.14 SETD5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Tracy Lester, the observed intellectual developmental disorder phenotype includes skeletal abnormalities ( at least 9 cases) and these might appear before ID. Hence, this gene can be promoted to green rating in the next GMS review.
Skeletal dysplasia v4.14 SETD5 Achchuthan Shanmugasundram Gene: setd5 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.13 SETD5 Achchuthan Shanmugasundram Classified gene: SETD5 as Amber List (moderate evidence)
Skeletal dysplasia v4.13 SETD5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Tracy Lester, the observed intellectual developmental disorder phenotype includes skeletal abnormalities ( at least 9 cases) and these might appear before ID. Hence, this gene can be promoted to green rating in the next GMS review.
Skeletal dysplasia v4.13 SETD5 Achchuthan Shanmugasundram Gene: setd5 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.12 SETD5 Achchuthan Shanmugasundram Phenotypes for gene: SETD5 were changed from Skeletal dysplasia; intellectual disability; developmental delay; facial dysmorphism to Intellectual developmental disorder, autosomal dominant 23, OMIM:615761; Skeletal dysplasia; intellectual disability; developmental delay; facial dysmorphism
Skeletal dysplasia v4.11 SETD5 Achchuthan Shanmugasundram Publications for gene: SETD5 were set to 28881385
Skeletal dysplasia v4.10 SETD5 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: SETD5.
Tag Q3_23_NHS_review tag was added to gene: SETD5.
Skeletal dysplasia v4.10 SETD5 Achchuthan Shanmugasundram reviewed gene: SETD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24680889, 28881385; Phenotypes: Intellectual developmental disorder, autosomal dominant 23, OMIM:615761; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v4.10 EN1 Eleanor Williams changed review comment from: The Genomics England clinical team confirm that the rating of this gene should currently be amber based on 1 case and a mouse model.; to: The Genomics England clinical team confirm that the rating of this gene should currently be amber based on 1 case and a mouse model. It has been additionally added to the 'Fetal anomalies' and 'Ataxia and cerebellar anomalies - narrow panel' panels based on the phenotype.

If more cases with intellectual disability/seizures are reported then it could be additionally added to those panels at that time.
Skeletal dysplasia v4.10 EN1 Eleanor Williams Tag watchlist tag was added to gene: EN1.
Skeletal dysplasia v4.10 EN1 Eleanor Williams commented on gene: EN1: The Genomics England clinical team confirm that the rating of this gene should currently be amber based on 1 case and a mouse model.
Skeletal dysplasia v4.10 SETD5 Tracy Lester gene: SETD5 was added
gene: SETD5 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: SETD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD5 were set to 28881385
Phenotypes for gene: SETD5 were set to Skeletal dysplasia; intellectual disability; developmental delay; facial dysmorphism
Penetrance for gene: SETD5 were set to Incomplete
Review for gene: SETD5 was set to GREEN
Added comment: This gene is associated with an autosomal dominant neurodevelopmental disorder characterised by developmental delay, intellectual disability, and variable dysmorphic and skeletal abnormalities. Expressivity is variable and non-penetrance has been reported. As the skeletal features might appear before the ID/DD I think this gene should be added to the SD panel. We recently found a pathogenic fs in this gene in a child with short stature, short long bones and facial dysmorphism but without mention of DD/ID; however case was only 10m old at referral.
Sources: NHS GMS
Skeletal dysplasia v4.10 FGF9 Eleanor Williams Phenotypes for gene: FGF9 were changed from ?Multiple synostoses syndrome type 3 612961 to Multiple synostoses syndrome 3, OMIM:612961; multiple synostoses syndrome 3, MONDO:0013064
Skeletal dysplasia v4.9 FGF9 Eleanor Williams Publications for gene: FGF9 were set to 19589401
Skeletal dysplasia v4.8 FGF9 Eleanor Williams Classified gene: FGF9 as Amber List (moderate evidence)
Skeletal dysplasia v4.8 FGF9 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber but with a recommendation for GREEN rating following GMS review as 4 unrelated cases with variants in FGF9 and a phenotype of multiple synostoses syndrome.
Skeletal dysplasia v4.8 FGF9 Eleanor Williams Gene: fgf9 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.7 FGF9 Eleanor Williams Tag watchlist was removed from gene: FGF9.
Tag Q2_23_promote_green tag was added to gene: FGF9.
Skeletal dysplasia v4.7 EN1 Eleanor Williams Classified gene: EN1 as Amber List (moderate evidence)
Skeletal dysplasia v4.7 EN1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. One patient with a loss of function variant in this gene and a skeletal phenotype reported, plus mouse model with this gene knocked out also shows a skeletal phenotype.

A further 3 patients with 27 and 63Kb deletions 300Kb upstream of this gene also show a skeletal phenotype and this appears to be due to ablation of a long non-coding RNA loci (in mice). However, at this distance it is unlikely to be detected by the Genomics England rare disease pipeline as being associated with EN1, and there are currently no regions on Skeletal dysplasia panel covering that area of chr 2. Therefore, at the present time this gene should be rated amber, following confirmation by the clinical team.
Skeletal dysplasia v4.7 EN1 Eleanor Williams Gene: en1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.6 EN1 Eleanor Williams commented on gene: EN1
Skeletal dysplasia v4.6 GPX4 Achchuthan Shanmugasundram Classified gene: GPX4 as Amber List (moderate evidence)
Skeletal dysplasia v4.6 GPX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence (>3 unrelated cases) available for this gene to be promoted to GREEN rating at the next major update.
Skeletal dysplasia v4.6 GPX4 Achchuthan Shanmugasundram Gene: gpx4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.5 GPX4 Achchuthan Shanmugasundram Publications for gene: GPX4 were set to 24706940; 32827718; 34931062
Skeletal dysplasia v4.5 GPX4 Achchuthan Shanmugasundram Publications for gene: GPX4 were set to 24706940
Skeletal dysplasia v4.4 GPX4 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: GPX4.
Skeletal dysplasia v4.4 GPX4 Achchuthan Shanmugasundram reviewed gene: GPX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24706940, 32827718, 34931062; Phenotypes: Spondylometaphyseal dysplasia, Sedaghatian type, OMIM:250220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.4 NMNAT1 Achchuthan Shanmugasundram Publications for gene: NMNAT1 were set to 32533184; 33668384
Skeletal dysplasia v4.4 NMNAT1 Achchuthan Shanmugasundram Publications for gene: NMNAT1 were set to 32533184; 33668384
Skeletal dysplasia v4.4 NMNAT1 Achchuthan Shanmugasundram Publications for gene: NMNAT1 were set to 32533184
Skeletal dysplasia v4.3 NMNAT1 Achchuthan Shanmugasundram Classified gene: NMNAT1 as Amber List (moderate evidence)
Skeletal dysplasia v4.3 NMNAT1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As two of the three reported families were distantly related, this gene should only be rated AMBER with the current evidence. However, 'watchlist' tag was added to review the rating in light of new evidence in the future.
Skeletal dysplasia v4.3 NMNAT1 Achchuthan Shanmugasundram Gene: nmnat1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.2 NMNAT1 Achchuthan Shanmugasundram commented on gene: NMNAT1: The 'cnv' tag was added as two of the reported cases harboured duplication variants in homozygous state and the third case harboured duplication variant together with a splicing variant.
Skeletal dysplasia v4.2 NMNAT1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: NMNAT1.
Tag cnv tag was added to gene: NMNAT1.
Skeletal dysplasia v4.2 NMNAT1 Achchuthan Shanmugasundram reviewed gene: NMNAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32533184, 33668384; Phenotypes: Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis, OMIM:619260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.2 PKDCC Eleanor Williams Classified gene: PKDCC as Green List (high evidence)
Skeletal dysplasia v4.2 PKDCC Eleanor Williams Added comment: Comment on list classification: Further expert review from Alistair Pagnamenta supports the green rating of this gene. No change in rating needed as is green already.
Skeletal dysplasia v4.2 PKDCC Eleanor Williams Gene: pkdcc has been classified as Green List (High Evidence).
Skeletal dysplasia v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Skeletal dysplasia v4.0 Eleanor Williams promoted panel to version 4.0
Skeletal dysplasia v3.13 EXT2 Sarah Leigh changed review comment from: Biallelic EXT2 variants are also reported in Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682. Table 2 in PMID: 30997052 highlights the phenotypic features of OMIM:616682. Scoliosis, which is relevant to this panel, is seen in 2/4 families reviewed in PMID: 30997052. If scoliosis is observed in more cases of OMIM:616682, then it would be appropriate to change the mode of inheritance of EXT2 to BOTH monoallelic and biallelic. The Watchlist tag has been added to this gene to reflect this situation.; to: Biallelic EXT2 variants are also reported in Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682. Table 2 in PMID: 30997052 highlights the phenotypic features of OMIM:616682. Scoliosis, which is relevant to this panel, is seen in 2/4 families reviewed in PMID: 30997052. If scoliosis is observed in more cases of OMIM:616682, then it would be appropriate to change the mode of inheritance of EXT2 to BOTH monoallelic and biallelic. The Watchlist_moi tag has been added to this gene to reflect this situation.
Skeletal dysplasia v3.13 EXT2 Sarah Leigh Tag watchlist_moi tag was added to gene: EXT2.
Skeletal dysplasia v3.13 EXT2 Sarah Leigh Phenotypes for gene: EXT2 were changed from Exostoses, multiple, type 2 133701 to Exostoses, multiple, type 2, OMIM:133701
Skeletal dysplasia v3.12 EXT2 Sarah Leigh edited their review of gene: EXT2: Added comment: Biallelic EXT2 variants are also reported in Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682. Table 2 in PMID: 30997052 highlights the phenotypic features of OMIM:616682. Scoliosis, which is relevant to this panel, is seen in 2/4 families reviewed in PMID: 30997052. If scoliosis is observed in more cases of OMIM:616682, then it would be appropriate to change the mode of inheritance of EXT2 to BOTH monoallelic and biallelic. The Watchlist tag has been added to this gene to reflect this situation.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v3.12 EXT2 Sarah Leigh Added comment: Comment on phenotypes: EXT2 variants are also reported in: Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682
Skeletal dysplasia v3.12 EXT2 Sarah Leigh Phenotypes for gene: EXT2 were changed from Exostoses, multiple, type 2 133701 to Exostoses, multiple, type 2 133701
Skeletal dysplasia v3.11 PKDCC Alistair Pagnamenta reviewed gene: PKDCC: Rating: GREEN; Mode of pathogenicity: None; Publications: https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14324; Phenotypes: rhizomelia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v3.11 KIF5B Achchuthan Shanmugasundram commented on gene: KIF5B: PMID:36018820 reported three additional unrelated cases with autosomal dominant KIF5B variants (p.Asn255del, p.Leu498Pro and p.Leu537Pro) resulting in a clinically wide phenotypic spectrum, ranging from dilated cardiomyopathy with adult-onset ophthalmoplegia and progressive skeletal myopathy to a neurodevelopmental condition characterised by severe hypotonia with or without seizures.
Skeletal dysplasia v3.11 KIF5B Achchuthan Shanmugasundram Classified gene: KIF5B as Amber List (moderate evidence)
Skeletal dysplasia v3.11 KIF5B Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN for skeletal dysplasia as there are four unrelated cases associated with monoallelic variants in KIF5B gene.
Skeletal dysplasia v3.11 KIF5B Achchuthan Shanmugasundram Gene: kif5b has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v3.10 KIF5B Achchuthan Shanmugasundram gene: KIF5B was added
gene: KIF5B was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to 35342932
Phenotypes for gene: KIF5B were set to kyphomelic dysplasia, MONDO:0008881
Review for gene: KIF5B was set to GREEN
Added comment: 4 individuals were reported with Kyphomelic dysplasia, which is characterised by severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. All these individuals harboured a de novo heterozygous missense variant in KIF5B gene ( two with c.272A>G (p.Lys91Arg), one with c.584C>A (p.Thr195Lys), and the other with c.701G>T(p.Gly234Val)). All three variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein.
Sources: Literature
Skeletal dysplasia v3.9 DDRGK1 Achchuthan Shanmugasundram Classified gene: DDRGK1 as Amber List (moderate evidence)
Skeletal dysplasia v3.9 DDRGK1 Achchuthan Shanmugasundram Gene: ddrgk1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v3.9 DDRGK1 Achchuthan Shanmugasundram Classified gene: DDRGK1 as Amber List (moderate evidence)
Skeletal dysplasia v3.9 DDRGK1 Achchuthan Shanmugasundram Gene: ddrgk1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v3.8 DDRGK1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: DDRGK1.
Skeletal dysplasia v3.8 DDRGK1 Achchuthan Shanmugasundram gene: DDRGK1 was added
gene: DDRGK1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: DDRGK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDRGK1 were set to 28263186; 35377455; 35670300; 36243336
Phenotypes for gene: DDRGK1 were set to Spondyloepimetaphyseal dysplasia, Shohat type, OMIM:602557
Review for gene: DDRGK1 was set to GREEN
Added comment: Comment on gene classification: This gene should be rated GREEN as it has been associated with Spondyloepimetaphyseal dysplasia, Shohat type from seven unrelated cases from multiple ethnicities and supported by functional studies.

PMID:28263186 reported six individuals from three different families of Iraqi Jewish descent (three patients from family 1 and one individual each from families 2-4) identified with homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK1 and presented with Shohat-type spondyloepimetaphyseal dysplasia (SEMD). It is a skeletal dysplasia that affects cartilage development.

PMID: 35670300 reported two unrelated cases of Moroccan descent identified with homozygous missense variant c.406G>A and presented with SEMD. PMID:36243336 reported an Omani female patient identified with the same homozygous variant as the Iraqi cases and was reported with SEMD.

In addition, studies on both zebrafish and mouse models confirms the physiological role of DDRGK1 in the development and maintenance of the growth plate cartilage and deficiency of DDRGK1 recapitulate the clinical phenotype of short stature and joint abnormalities observed in patients with Shohat type SEMD (PMID:28263186; PMID:35377455).

This gene has been associated with relevant phenotype in OMIM (MIM #602557), but not in Gene2Phenotype.
Sources: Literature
Skeletal dysplasia v3.7 WNT1 Achchuthan Shanmugasundram Publications for gene: WNT1 were set to 23499309; 23499310; 23434763; 23656646
Skeletal dysplasia v3.7 WNT1 Achchuthan Shanmugasundram Publications for gene: WNT1 were set to 34875064
Skeletal dysplasia v3.6 WNT1 Achchuthan Shanmugasundram Publications for gene: WNT1 were set to 34875064
Skeletal dysplasia v3.6 WNT1 Achchuthan Shanmugasundram Publications for gene: WNT1 were set to
Skeletal dysplasia v3.5 DVL2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DVL2.
Skeletal dysplasia v3.5 DROSHA Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DROSHA.
Skeletal dysplasia v3.5 HHAT Eleanor Williams Tag Q4_21_rating was removed from gene: HHAT.
Skeletal dysplasia v3.5 HHAT Eleanor Williams changed review comment from: The rating of this gene has been updated to greenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 AFF3 Eleanor Williams Tag Q2_22_rating was removed from gene: AFF3.
Skeletal dysplasia v3.5 AFF3 Eleanor Williams changed review comment from: The rating of this gene has been updated to greenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 STT3A Eleanor Williams Tag Q3_22_rating was removed from gene: STT3A.
Tag Q3_22_NHS_review was removed from gene: STT3A.
Skeletal dysplasia v3.5 STT3A Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 DVL2 Eleanor Williams Tag Q2_21_NHS_review was removed from gene: DVL2.
Tag Q2_22_rating was removed from gene: DVL2.
Tag Q2_22_expert_review was removed from gene: DVL2.
Skeletal dysplasia v3.5 DVL2 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 MYH3 Eleanor Williams Tag Q3_22_rating was removed from gene: MYH3.
Skeletal dysplasia v3.5 MYH3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 PRKAR1A Eleanor Williams Tag Q2_22_MOI was removed from gene: PRKAR1A.
Skeletal dysplasia v3.5 PRKAR1A Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 ANO5 Eleanor Williams Tag Q1_22_MOI was removed from gene: ANO5.
Skeletal dysplasia v3.5 ANO5 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 COL1A2 Eleanor Williams Tag Q2_22_MOI was removed from gene: COL1A2.
Tag Q2_22_expert_review was removed from gene: COL1A2.
Skeletal dysplasia v3.5 COL1A2 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 LTBP3 Eleanor Williams Tag Q1_22_NHS_review was removed from gene: LTBP3.
Tag Q1_22_MOI was removed from gene: LTBP3.
Skeletal dysplasia v3.5 LTBP3 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 COPB2 Eleanor Williams Tag watchlist_moi was removed from gene: COPB2.
Skeletal dysplasia v3.5 COPB2 Eleanor Williams Tag Q1_22_MOI was removed from gene: COPB2.
Skeletal dysplasia v3.5 COPB2 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 COL9A1 Eleanor Williams Tag Q4_21_MOI was removed from gene: COL9A1.
Skeletal dysplasia v3.5 COL9A1 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 DROSHA Eleanor Williams Tag Q2_22_rating was removed from gene: DROSHA.
Skeletal dysplasia v3.5 DROSHA Eleanor Williams changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsamber. The reviewers note that there is insufficient evidence for link to skeletal dysplasia, primarily neurological. Only 2 cases with missense variants, minor skeletal anomalies and link to gene not proven.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The reviewers note that there is insufficient evidence for link to skeletal dysplasia, primarily neurological. Only 2 cases with missense variants, minor skeletal anomalies and link to gene not proven.
Skeletal dysplasia v3.5 CSNK1G1 Eleanor Williams Tag Q1_22_rating was removed from gene: CSNK1G1.
Skeletal dysplasia v3.5 HHAT Eleanor Williams commented on gene: HHAT: The rating of this gene has been updated to greenfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 AFF3 Eleanor Williams reviewed gene: AFF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v3.5 STT3A Eleanor Williams reviewed gene: STT3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v3.5 DVL2 Eleanor Williams edited their review of gene: DVL2: Added comment: The rating of this gene has been updated togreenand the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Skeletal dysplasia v3.5 MYH3 Eleanor Williams commented on gene: MYH3: The rating of this gene has been updated togreenand the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 PRKAR1A Eleanor Williams commented on gene: PRKAR1A: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 ANO5 Eleanor Williams commented on gene: ANO5: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 COL1A2 Eleanor Williams commented on gene: COL1A2: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 LTBP3 Eleanor Williams commented on gene: LTBP3: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 COPB2 Eleanor Williams commented on gene: COPB2: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 COL9A1 Eleanor Williams commented on gene: COL9A1: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 DROSHA Eleanor Williams reviewed gene: DROSHA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v3.5 CSNK1G1 Eleanor Williams reviewed gene: CSNK1G1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v3.4 STT3A Eleanor Williams Source Expert Review Green was added to STT3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v3.4 PRKAR1A Eleanor Williams Mode of inheritance for gene PRKAR1A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v3.4 MYH3 Eleanor Williams Source Expert Review Green was added to MYH3.
Source NHS GMS was added to MYH3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v3.4 LTBP3 Eleanor Williams Mode of inheritance for gene LTBP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v3.4 HHAT Eleanor Williams Source Expert Review Green was added to HHAT.
Source NHS GMS was added to HHAT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v3.4 DVL2 Eleanor Williams Source Expert Review Green was added to DVL2.
Source NHS GMS was added to DVL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v3.4 COPB2 Eleanor Williams Mode of inheritance for gene COPB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v3.4 COL9A1 Eleanor Williams Mode of inheritance for gene COL9A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v3.4 COL1A2 Eleanor Williams Mode of inheritance for gene COL1A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v3.4 ANO5 Eleanor Williams Mode of inheritance for gene ANO5 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v3.4 AFF3 Eleanor Williams Source Expert Review Green was added to AFF3.
Source NHS GMS was added to AFF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v3.3 GHR Arina Puzriakova Phenotypes for gene: GHR were changed from {Hypercholesterolemia, familial, modification of}, 143890; Growth hormone insensitivity; Short stature, 604271; increased responsiveness to growth hormone 604271; Increased responsiveness to growth hormone; Laron dwarfism, 262500; Proportionate Short Stature/Small for Gestational Age to Laron dwarfism, OMIM:262500; Growth hormone insensitivity, partial, OMIM:604271; Increased responsiveness to growth hormone, OMIM:604271
Skeletal dysplasia v3.2 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from Langer mesomelic dysplasia 249700; Short stature, idiopathic familial 300582; Leri-Weill dyschondrosteosis 127300 to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582; Dorsolateral bowed, short radii; Bowing and curving of radius; Radioulnar shortening
Skeletal dysplasia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Skeletal dysplasia v3.0 Catherine Snow promoted panel to version 3.0
Skeletal dysplasia v2.228 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Dyskeratosis congenita, autosomal dominant 2 and autosomal recessive 4 613989 to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Skeletal dysplasia v2.227 RAD21 Arina Puzriakova Publications for gene: RAD21 were set to 22633399; 30716475; 24378232; 27882533; 27620904
Skeletal dysplasia v2.226 RAD21 Arina Puzriakova Classified gene: RAD21 as Amber List (moderate evidence)
Skeletal dysplasia v2.226 RAD21 Arina Puzriakova Added comment: Comment on list classification: Although limb abnormalities are a common feature of CdLS, only minor skeletal anomalies are associated with RAD21 variants. Other prominent features such as ID are more likely to prompt testing and therefore maintaining the Amber rating on skeletal panels for now.
Skeletal dysplasia v2.226 RAD21 Arina Puzriakova Gene: rad21 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.225 RAD21 Arina Puzriakova reviewed gene: RAD21: Rating: ; Mode of pathogenicity: None; Publications: 32193685; Phenotypes: Cornelia de Lange syndrome 4, OMIM:614701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.225 RAD21 Arina Puzriakova Phenotypes for gene: RAD21 were changed from Cornelia de Lange syndrome 4 614701 to Cornelia de Lange syndrome 4, OMIM:614701
Skeletal dysplasia v2.224 ARSK Arina Puzriakova Classified gene: ARSK as Amber List (moderate evidence)
Skeletal dysplasia v2.224 ARSK Arina Puzriakova Added comment: Comment on list classification: Rating Amber awaiting further cases.
Skeletal dysplasia v2.224 ARSK Arina Puzriakova Gene: arsk has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.223 ARSK Arina Puzriakova gene: ARSK was added
gene: ARSK was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSK were set to 34916232
Phenotypes for gene: ARSK were set to Mucopolysaccharidoses with short stature, coarse facial features and dysostosis multiplex
Review for gene: ARSK was set to AMBER
Added comment: Verheyen et al. 2022 (PMID: 34916232) reported four affected individuals of two unrelated consanguineous families with homozygous variants c.250C>T, p.(Arg84Cys) and c.560T>A, p.(Leu187Ter) in ARSK, respectively. Patients were affected with skeletal dysplasia, resembling spondyloepiphysial dysplasia. Reverse phenotyping in two individuals from one family revealed additional cardiac and ophthalmological abnormalities.
Sources: Literature
Skeletal dysplasia v2.222 GNAS Sarah Leigh Tag Q4_22_MOI tag was added to gene: GNAS.
Skeletal dysplasia v2.222 GNAS Sarah Leigh edited their review of gene: GNAS: Added comment: Disease causing variants in the GNAS locus have differing expression panels. Pseudohypothyroidism Ia, Ib & Ic are all caused by GNAS variants arising in the maternal alleles, therefore, the mode of inheritance (MOI) for GNAS in these conditions should be monoallelic maternally imprinted. Pseudopseudohypoparathyroidism, OMIM:612463 and Osseous heteroplasia, progressive, OMIM:166350 are associated with variants in the paternal alleles therefore, the mode of inheritance for GNAS in these conditions should be monoallelic paternally imprinted. Because the Skeletal dysplasia panel is representing various phenotypes, the MOI has been set to monoallelic, imprinted status unknown.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.222 GNAS Sarah Leigh Phenotypes for gene: GNAS were changed from Pseudohypoparathyroidism Ia 103580; Pseudopseudohypoparathyroidism 612463; Osseous heteroplasia, progressive 166350; Pseudohypoparathyroidism Ib 603233; Pseudohypoparathyroidism Ic 612462; ACTH-independent macronodular adrenal hyperplasia 219080 IC; McCune-Albright syndrome, somatic, mosaic 174800 to Pseudohypoparathyroidism Ia, OMIM:103580; pseudohypoparathyroidism type 1A, MONDO:0007078; Pseudohypoparathyroidism Ib, OMIM:603233; pseudohypoparathyroidism type 1B, MONDO:0011301; Pseudohypoparathyroidism Ic, OMIM:612462; pseudohypoparathyroidism type 1C, MONDO:0012911; McCune-Albright syndrome, somatic, mosaic, OMIM:174800; panostotic fibrous dysplasia, MONDO:0043168; Osseous heteroplasia, progressive, OMIM:166350; ACTH-independent macronodular adrenal hyperplasia. OMIM:219080; ACTH-independent macronodular adrenal hyperplasia 1, MONDO:0020735; Pseudopseudohypoparathyroidism, OMIM:612463; pseudopseudohypoparathyroidism, MONDO:0012912
Skeletal dysplasia v2.221 KIF24 Arina Puzriakova Classified gene: KIF24 as Amber List (moderate evidence)
Skeletal dysplasia v2.221 KIF24 Arina Puzriakova Added comment: Comment on list classification: This gene should be promoted to Green at the next GMS panel update, on the basis of three unrelated cases harbouring distinct biallelic variants in this gene, all presenting with variable skeletal manifestations.
Skeletal dysplasia v2.221 KIF24 Arina Puzriakova Gene: kif24 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.220 KIF24 Arina Puzriakova gene: KIF24 was added
gene: KIF24 was added to Skeletal dysplasia. Sources: Literature
Q4_22_promote_green tags were added to gene: KIF24.
Mode of inheritance for gene: KIF24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF24 were set to 35748595
Phenotypes for gene: KIF24 were set to Skeletal dysplasia
Review for gene: KIF24 was set to GREEN
Added comment: Reilly et al., 2022 (PMID: 35748595) identified six individuals from three unrelated families affected by a spectrum of skeletal abnormalities ranging from a lethal fetal skeletal ciliopathy to acromesomelic skeletal dysplasia and a less severe spondylometaphyseal dysplasia. All subjects harboured different biallelic missense variants in KIF24 which segregated with the phenotype. In vitro studies showed that ciliogenesis and cytokinesis were severely affected in amnioblasts of one affected fetus.
Sources: Literature
Skeletal dysplasia v2.219 ROR2 Arina Puzriakova Phenotypes for gene: ROR2 were changed from Brachydactyly, type B1 113000; Robinow syndrome, autosomal recessive 268310 to Brachydactyly, type B1, OMIM:113000 (AD); Robinow syndrome, autosomal recessive, OMIM:268310 (AR)
Skeletal dysplasia v2.218 TGFB1 Arina Puzriakova Phenotypes for gene: TGFB1 were changed from Camurati-Engelmann disease 131300; Camurati-Engelmann disease 131300 to Camurati-Engelmann disease, OMIM:131300
Skeletal dysplasia v2.217 MYH3 Eleanor Williams Phenotypes for gene: MYH3 were changed from Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, OMIM:178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, OMIM:618469 to Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, OMIM:178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, OMIM:618469; contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, MONDO:0008338
Skeletal dysplasia v2.216 MYH3 Eleanor Williams Phenotypes for gene: MYH3 were changed from to Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, OMIM:178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, OMIM:618469
Skeletal dysplasia v2.215 MYH3 Eleanor Williams Classified gene: MYH3 as Amber List (moderate evidence)
Skeletal dysplasia v2.215 MYH3 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber but with a green recommendation following GMS review.
Skeletal dysplasia v2.215 MYH3 Eleanor Williams Gene: myh3 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.214 MYH3 Eleanor Williams Tag Q3_22_rating tag was added to gene: MYH3.
Skeletal dysplasia v2.214 MYH3 Eleanor Williams Publications for gene: MYH3 were set to 35169139
Skeletal dysplasia v2.213 MYH3 Eleanor Williams reviewed gene: MYH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25957469, 27381093, 28205584, 29314551, 29805041, 35169139; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.213 NRCAM Sarah Leigh Tag watchlist tag was added to gene: NRCAM.
Skeletal dysplasia v2.213 NRCAM Sarah Leigh Deleted their comment
Skeletal dysplasia v2.213 NRCAM Sarah Leigh Tag Q3_22_rating was removed from gene: NRCAM.
Tag Q3_22_MOI was removed from gene: NRCAM.
Skeletal dysplasia v2.213 NRCAM Sarah Leigh Entity copied from Intellectual disability v3.1716
Skeletal dysplasia v2.213 NRCAM Sarah Leigh gene: NRCAM was added
gene: NRCAM was added to Skeletal dysplasia. Sources: Literature,Expert Review Amber
Q3_22_rating, Q3_22_MOI tags were added to gene: NRCAM.
Mode of inheritance for gene: NRCAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRCAM were set to 35108495
Phenotypes for gene: NRCAM were set to Neurodevelopmental disorder with neuromuscular and skeletal abnormalities, OMIM:619833
Penetrance for gene: NRCAM were set to Complete
Skeletal dysplasia v2.212 MYH3 Dmitrijs Rots gene: MYH3 was added
gene: MYH3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: MYH3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYH3 were set to 35169139
Review for gene: MYH3 was set to GREEN
Added comment: 17 individuals with variable vertebral and spine anomalies, as well as short stature reported in 35169139. Pathogenic variants in MYH3 cause not only Arthrogryposis.
Sources: Literature
Skeletal dysplasia v2.212 HEATR3 Sarah Leigh Tag watchlist tag was added to gene: HEATR3.
Skeletal dysplasia v2.212 HEATR3 Sarah Leigh edited their review of gene: HEATR3: Added comment: After consultation with Helen Brittain (Clinical Fellow, Genomics England), is was concluded that there is not enough evidence for skeletal dysplasia in the cases reported in PMID: 35213692 for HEATR3 to be rated green on this panel, as the height of the affected individuals ranged from <–4 SD to normal.; Changed rating: AMBER
Skeletal dysplasia v2.212 HEATR3 Sarah Leigh Tag Q3_22_rating was removed from gene: HEATR3.
Tag Q3_22_MOI was removed from gene: HEATR3.
Skeletal dysplasia v2.212 HEATR3 Sarah Leigh Entity copied from Rare anaemia v1.42
Skeletal dysplasia v2.212 HEATR3 Sarah Leigh gene: HEATR3 was added
gene: HEATR3 was added to Skeletal dysplasia. Sources: Literature,Expert Review Amber
Q3_22_rating, Q3_22_MOI tags were added to gene: HEATR3.
Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR3 were set to 35213692
Phenotypes for gene: HEATR3 were set to Anemia; Thrombocytopenia; Growth delay; Short stature; Abnormality of the skeletal system; Abnormality of finger; Abnormality of the thumb; Intellectual disability; Obesity; Abnormality of the face
Penetrance for gene: HEATR3 were set to Complete
Skeletal dysplasia v2.211 SLC35B2 Sarah Leigh Entity copied from Intellectual disability v3.1672
Skeletal dysplasia v2.211 SLC35B2 Sarah Leigh gene: SLC35B2 was added
gene: SLC35B2 was added to Skeletal dysplasia. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: SLC35B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35B2 were set to 35325049
Phenotypes for gene: SLC35B2 were set to Abnormality of the skeletal system; Short long bone; Short stature; Abnormality of epiphysis morphology; Scoliosis; Multiple joint dislocation; Global develpmental delay; Intellectual disability; CNS hypomyelination; Abnormality of the corpus callosum; Cerebral atrophy; Abnormality of the amniotic fluid
Penetrance for gene: SLC35B2 were set to Complete
Skeletal dysplasia v2.210 STT3A Arina Puzriakova Phenotypes for gene: STT3A were changed from Short stature; skeletal defects; Intellectual disability; Speech delay; macrocephaly; dysmorphism to Congenital disorder of glycosylation, type Iw, autosomal dominant, OMIM:619714
Skeletal dysplasia v2.209 STT3A Arina Puzriakova Classified gene: STT3A as Amber List (moderate evidence)
Skeletal dysplasia v2.209 STT3A Arina Puzriakova Added comment: Comment on list classification: Congenital disorder of glycosylation due to monoallelic variants in STT3A has been identified in at least 16 patients from 9 families (PMID: 34653363). Phenotypes included skeletal abnormalities in 10/16 subjects. Overall this supports a Green gene rating with a 'monoallelic' MOI on this panel at the next GMS panel review.
Skeletal dysplasia v2.209 STT3A Arina Puzriakova Gene: stt3a has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.208 STT3A Arina Puzriakova Tag Q3_22_rating tag was added to gene: STT3A.
Tag Q3_22_NHS_review tag was added to gene: STT3A.
Skeletal dysplasia v2.208 SNRPB Arina Puzriakova commented on gene: SNRPB
Skeletal dysplasia v2.208 FGFR2 Arina Puzriakova commented on gene: FGFR2
Skeletal dysplasia v2.208 COL11A2 Arina Puzriakova commented on gene: COL11A2
Skeletal dysplasia v2.207 STT3A Tracy Lester gene: STT3A was added
gene: STT3A was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: STT3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STT3A were set to 34653363
Phenotypes for gene: STT3A were set to Short stature; skeletal defects; Intellectual disability; Speech delay; macrocephaly; dysmorphism
Penetrance for gene: STT3A were set to unknown
Mode of pathogenicity for gene: STT3A was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: STT3A was set to GREEN
Added comment: A recent paper has shown that heterozygous missense variants in the active site cause a disorder of glycosylation associated with short stature and skeletal defects in a majority of individuals. The gene is already green on the ID panel for AR condition but new review has been added to change to AD as well. The recessive disorder associated with this gene in primarily neurological so this inheritance model is not relevant in the context of skeletal dysplasia
Sources: NHS GMS
Skeletal dysplasia v2.207 DROSHA Sarah Leigh Entity copied from Genetic epilepsy syndromes v2.526
Skeletal dysplasia v2.207 DROSHA Sarah Leigh gene: DROSHA was added
gene: DROSHA was added to Skeletal dysplasia. Sources: Expert Review Amber,Literature
locus-type-rna-micro, Q2_22_rating tags were added to gene: DROSHA.
Mode of inheritance for gene: DROSHA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DROSHA were set to 35405010
Phenotypes for gene: DROSHA were set to Global developmental delay; Intellectual disability; Seizures; Cerebral white matter atrophy; Abnormality of the corpus callosum; Abnormality of movement; Stereotypic behavior; Abnormality of head or neck; Short foot
Penetrance for gene: DROSHA were set to unknown
Mode of pathogenicity for gene: DROSHA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Skeletal dysplasia v2.206 IMPAD1 Arina Puzriakova commented on gene: IMPAD1
Skeletal dysplasia v2.206 IMPAD1 Arina Puzriakova Tag new-gene-name tag was added to gene: IMPAD1.
Skeletal dysplasia v2.206 WBP11 Arina Puzriakova Tag gene-checked tag was added to gene: WBP11.
Skeletal dysplasia v2.206 CSNK1G1 Sarah Leigh Tag gene-checked tag was added to gene: CSNK1G1.
Skeletal dysplasia v2.206 KDELR2 Arina Puzriakova Phenotypes for gene: KDELR2 were changed from Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms; Osteogenesis imperfecta to Osteogenesis imperfecta, type XXI, OMIM:619131; Increased susceptibility to fractures; Joint hypermobility; Scoliosis; Bowing of the legs and arms
Skeletal dysplasia v2.205 COL1A2 Eleanor Williams Phenotypes for gene: COL1A2 were changed from Ehlers-Danlos syndrome, cardiac valvular form 225320; Ehlers-Danlos syndrome, type VIIB 130060; Osteogenesis imperfecta, type II 166210; Osteogenesis imperfecta, type III 259420; Osteogenesis imperfecta, type IV 166220 to Ehlers-Danlos syndrome, cardiac valvular form, OMIM:225320; Ehlers-Danlos syndrome, type VIIB, OMIM:130060; Osteogenesis imperfecta, type II, OMIM:166210; Osteogenesis imperfecta, type III, OMIM:259420; Osteogenesis imperfecta, type IV, OMIM:166220
Skeletal dysplasia v2.204 COL1A2 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the mode of inheritance as Both mono and biallelic for now, but adding a tag for GMS review. Only Ehlers-Danlos syndrome, cardiac valvular type is biallelic, and this phenotype may not be within scope of the Skeletal dysplasia panel.
Skeletal dysplasia v2.204 COL1A2 Eleanor Williams Mode of inheritance for gene: COL1A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.203 IHH Arina Puzriakova Phenotypes for gene: IHH were changed from Acrocapitofemoral dysplasia 607778; Brachydactyly, type A1 112500 to Acrocapitofemoral dysplasia, OMIM:607778; Brachydactyly, type A1, OMIM:112500
Skeletal dysplasia v2.202 COL1A2 Eleanor Williams Tag Q2_22_MOI tag was added to gene: COL1A2.
Tag Q2_22_expert_review tag was added to gene: COL1A2.
Skeletal dysplasia v2.202 DVL2 Eleanor Williams Classified gene: DVL2 as Amber List (moderate evidence)
Skeletal dysplasia v2.202 DVL2 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, but with a recommendation for consideration for GREEN rating following GMS review. Although only 1 case has been reported, supporting evidence comes from canine data and from the fact that similar causative variants associated with Robinow syndrome have been found in the other two Dishevelled paralogs.
Skeletal dysplasia v2.202 DVL2 Eleanor Williams Gene: dvl2 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.201 DVL2 Eleanor Williams Tag Q2_22_expert_review tag was added to gene: DVL2.
Skeletal dysplasia v2.201 DVL2 Eleanor Williams Publications for gene: DVL2 were set to PMID: 35047859
Skeletal dysplasia v2.200 DVL2 Eleanor Williams Tag Q2_21_NHS_review tag was added to gene: DVL2.
Tag Q2_22_rating tag was added to gene: DVL2.
Skeletal dysplasia v2.200 DVL2 Eleanor Williams reviewed gene: DVL2: Rating: ; Mode of pathogenicity: None; Publications: 35047859, 33599851, 30521570; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v2.200 DVL2 Eleanor Williams Phenotypes for gene: DVL2 were changed from autosomal dominant Robinow sydrome to autosomal dominant Robinow sydrome; Robinow syndrome, MONDO:0019978
Skeletal dysplasia v2.199 BMP2 Eleanor Williams Tag cnv tag was added to gene: BMP2.
Skeletal dysplasia v2.199 BMP2 Eleanor Williams commented on gene: BMP2: There is currently no ClinGen curated CNV covering this region on chromosome 20.
Skeletal dysplasia v2.199 PRKAR1A Eleanor Williams Added comment: Comment on mode of inheritance: No reports of biallelic cases found so recommendation is to change the mode of inheritance to monoallelic only after GMS review.
Skeletal dysplasia v2.199 PRKAR1A Eleanor Williams Mode of inheritance for gene: PRKAR1A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.198 PRKAR1A Eleanor Williams Phenotypes for gene: PRKAR1A were changed from Acrodysostosis 1, with or without hormone resistance 101800; Myxoma, intracardiac 255960; Pigmented nodular adrenocortical disease, primary, 1 610489 to Acrodysostosis 1, with or without hormone resistance, OMIM:101800
Skeletal dysplasia v2.197 PRKAR1A Eleanor Williams Publications for gene: PRKAR1A were set to
Skeletal dysplasia v2.196 PRKAR1A Eleanor Williams Mode of pathogenicity for gene: PRKAR1A was changed from to Other
Skeletal dysplasia v2.195 PRKAR1A Eleanor Williams Tag Q2_22_MOI tag was added to gene: PRKAR1A.
Skeletal dysplasia v2.195 PRKAR1A Eleanor Williams edited their review of gene: PRKAR1A: Added comment: Looking at the mode of inheritance of this gene on the Skeletal dysplasia panel where it is Both mono and bi-allelic.

In OMIM and Gene2Phenotype the relevant phenotypes of Acrodysostosis 1, with or without hormone resistance, OMIM:101800 and ACRODYSOSTOSIS respectively are listed with autosomal dominant/monoallelic inheritance.

There are several reports of heterozygous variants in PRKAR1A in patients with Acrodysostosis (PMIDs: 21651393, 22464250, 22464252, 28804209, 23425300, 25075981, 26763073). No reports of biallelic variants were found in a search of PubMed. Therefore the recommendation is for the mode of inheritance to be changed to monoallelic only.; Changed mode of pathogenicity: Other; Changed publications to: 21651393, 22464250, 22464252, 28804209, 23425300, 25075981, 26763073; Changed phenotypes to: Acrodysostosis 1, with or without hormone resistance, OMIM:101800; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.195 LIFR Eleanor Williams Phenotypes for gene: LIFR were changed from Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome 601559 to Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, OMIM:601559
Skeletal dysplasia v2.194 AFF3 Arina Puzriakova Classified gene: AFF3 as Amber List (moderate evidence)
Skeletal dysplasia v2.194 AFF3 Arina Puzriakova Added comment: Comment on list classification: Upgrading from Red to Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Skeletal dysplasia v2.194 AFF3 Arina Puzriakova Gene: aff3 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.193 AFF3 Arina Puzriakova Tag Q2_22_rating tag was added to gene: AFF3.
Skeletal dysplasia v2.193 AFF3 Arina Puzriakova reviewed gene: AFF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18616733, 31388108, 33961779; Phenotypes: KINSSHIP syndrome, OMIM:619297; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.193 AFF3 Arina Puzriakova Publications for gene: AFF3 were set to
Skeletal dysplasia v2.192 AFF3 Arina Puzriakova Mode of inheritance for gene: AFF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.191 AFF3 Arina Puzriakova Phenotypes for gene: AFF3 were changed from No OMIM or G2P phenotype to KINSSHIP syndrome, OMIM:619297
Skeletal dysplasia v2.190 ANO5 Sarah Leigh Tag Q1_22_MOI tag was added to gene: ANO5.
Skeletal dysplasia v2.190 DVL2 Michael Oldridge gene: DVL2 was added
gene: DVL2 was added to Skeletal dysplasia. Sources: Expert Review
Mode of inheritance for gene: DVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DVL2 were set to PMID: 35047859
Phenotypes for gene: DVL2 were set to autosomal dominant Robinow sydrome
Penetrance for gene: DVL2 were set to Complete
Mode of pathogenicity for gene: DVL2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: DVL2 was set to GREEN
Added comment: De novo fs variant in final exon of DVL2 identified in patient with clinical diagnosis of Robinow syndrome. This leads to a 103 residue missense tail extending beyond the WT stop codon. A number of similar fs variants have been identified in DVL1 and DVL3 leading to autosomal dominant Robinow syndrome; these variants also lead to extended missense tails and are therefore thought to act via a very specific gain of function mechanism (LOF variants in these genes do not lead to Robinow). DVL1, 2 and 3 share considerable homology (59-67%) and have overlapping function during development.
Only reported in 1 case but the very specific nature of the mutation explains rareity. Should be tested as Green.
Sources: Expert Review
Skeletal dysplasia v2.190 ISCA-37441-Loss Eleanor Williams commented on Region: ISCA-37441-Loss: The required percent of overlap for this region has been changed from 80% to 60% following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.190 ISCA-37434-Loss Arina Puzriakova commented on Region: ISCA-37434-Loss
Skeletal dysplasia v2.190 ISCA-37501-Loss Arina Puzriakova commented on Region: ISCA-37501-Loss
Skeletal dysplasia v2.190 ISCA-37418-Loss Arina Puzriakova commented on Region: ISCA-37418-Loss
Skeletal dysplasia v2.190 ISCA-37406-Loss Ivone Leong commented on Region: ISCA-37406-Loss
Skeletal dysplasia v2.190 ISCA-37394-Loss Ivone Leong commented on Region: ISCA-37394-Loss
Skeletal dysplasia v2.190 ISCA-37394-Loss Arina Puzriakova Required Overlap Percentage for ISCA-37394-Loss was changed from 80 to 60.
Skeletal dysplasia v2.190 ISCA-37434-Loss Arina Puzriakova Required Overlap Percentage for ISCA-37434-Loss was changed from 80 to 60.
Skeletal dysplasia v2.190 ISCA-37501-Loss Arina Puzriakova Triplosensitivity Score for ISCA-37501-Loss was changed from None to .
Required Overlap Percentage for ISCA-37501-Loss was changed from 80 to 60.
Skeletal dysplasia v2.190 ISCA-37418-Loss Arina Puzriakova GRCh38 position for ISCA-37418-Loss was changed from 16853797-20316338 to 16906714-20309889.
Required Overlap Percentage for ISCA-37418-Loss was changed from 80 to 60.
Skeletal dysplasia v2.190 ISCA-37406-Loss Arina Puzriakova Required Overlap Percentage for ISCA-37406-Loss was changed from 80 to 60.
Skeletal dysplasia v2.190 ISCA-37441-Loss Arina Puzriakova Required Overlap Percentage for ISCA-37441-Loss was changed from 80 to 60.
Skeletal dysplasia v2.189 ATXN10_ATTCT Ivone Leong commented on STR: ATXN10_ATTCT
Skeletal dysplasia v2.187 ATXN10_ATTCT Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33.
Source NHS GMS was added to STR: ATXN10_ATTCT.
Skeletal dysplasia v2.186 SNRPB Eleanor Williams commented on gene: SNRPB: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.186 FGFR2 Eleanor Williams commented on gene: FGFR2: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.186 COL11A2 Eleanor Williams commented on gene: COL11A2: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.185 SNRPB Eleanor Williams Mode of inheritance for gene SNRPB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.185 FGFR2 Eleanor Williams Mode of inheritance for gene FGFR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.185 COL11A2 Eleanor Williams Mode of inheritance for gene COL11A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.184 PRKG2 Eleanor Williams Tag Q4_21_NHS_review was removed from gene: PRKG2.
Skeletal dysplasia v2.184 MBTPS2 Eleanor Williams Tag Q3_21_rating was removed from gene: MBTPS2.
Tag Q3_21_expert_review was removed from gene: MBTPS2.
Skeletal dysplasia v2.184 MESD Eleanor Williams Tag Q3_21_rating was removed from gene: MESD.
Tag Q3_21_NHS_review was removed from gene: MESD.
Skeletal dysplasia v2.184 ZNF687 Eleanor Williams Tag Q4_21_rating was removed from gene: ZNF687.
Tag Q4_21_NHS_review was removed from gene: ZNF687.
Skeletal dysplasia v2.184 WBP11 Eleanor Williams Tag Q2_21_rating was removed from gene: WBP11.
Skeletal dysplasia v2.184 UNC45A Eleanor Williams Tag Q3_21_rating was removed from gene: UNC45A.
Tag Q3_21_NHS_review was removed from gene: UNC45A.
Skeletal dysplasia v2.184 UFSP2 Eleanor Williams Tag Q2_21_rating was removed from gene: UFSP2.
Skeletal dysplasia v2.184 SGMS2 Eleanor Williams Tag Q3_21_rating was removed from gene: SGMS2.
Skeletal dysplasia v2.184 SCUBE3 Eleanor Williams Tag Q2_21_rating was removed from gene: SCUBE3.
Skeletal dysplasia v2.184 MYO18B Eleanor Williams Tag Q3_21_rating was removed from gene: MYO18B.
Skeletal dysplasia v2.184 LTBP1 Eleanor Williams Tag Q2_21_rating was removed from gene: LTBP1.
Skeletal dysplasia v2.184 LRRK1 Eleanor Williams Tag Q3_21_rating was removed from gene: LRRK1.
Tag Q3_21_NHS_review was removed from gene: LRRK1.
Skeletal dysplasia v2.184 FBN2 Eleanor Williams Tag Q2_21_MOI was removed from gene: FBN2.
Skeletal dysplasia v2.184 DSPP Eleanor Williams Tag Q3_21_expert_review was removed from gene: DSPP.
Skeletal dysplasia v2.184 DLX5 Eleanor Williams Tag Q3_21_MOI was removed from gene: DLX5.
Tag Q3_21_NHS_review was removed from gene: DLX5.
Skeletal dysplasia v2.184 COPB2 Eleanor Williams commented on gene: COPB2: Updating the mode of inheritance of this gene to both Mono and biallelic should be considered
Skeletal dysplasia v2.184 COPB2 Eleanor Williams Tag Q3_21_rating was removed from gene: COPB2.
Tag Q1_22_MOI tag was added to gene: COPB2.
Skeletal dysplasia v2.184 ARCN1 Eleanor Williams Tag Q3_21_rating was removed from gene: ARCN1.
Skeletal dysplasia v2.184 ZNF687 Eleanor Williams commented on gene: ZNF687: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 WBP11 Eleanor Williams commented on gene: WBP11: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 UNC45A Eleanor Williams commented on gene: UNC45A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 UFSP2 Eleanor Williams commented on gene: UFSP2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 SGMS2 Eleanor Williams commented on gene: SGMS2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 SCUBE3 Eleanor Williams commented on gene: SCUBE3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 MYO18B Eleanor Williams commented on gene: MYO18B
Skeletal dysplasia v2.184 MESD Eleanor Williams commented on gene: MESD: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 MBTPS2 Eleanor Williams commented on gene: MBTPS2: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed. It has been agreed to keep this gene as amber at this time.
Skeletal dysplasia v2.184 LTBP1 Eleanor Williams commented on gene: LTBP1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 LRRK1 Eleanor Williams commented on gene: LRRK1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 FBN2 Eleanor Williams commented on gene: FBN2: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 DSPP Eleanor Williams commented on gene: DSPP: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 DLX5 Eleanor Williams commented on gene: DLX5: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 COPB2 Eleanor Williams commented on gene: COPB2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.184 ARCN1 Eleanor Williams commented on gene: ARCN1
Skeletal dysplasia v2.183 ZNF687 Eleanor Williams Source Expert Review Green was added to ZNF687.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 WBP11 Eleanor Williams Source Expert Review Green was added to WBP11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 UNC45A Eleanor Williams Source Expert Review Green was added to UNC45A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 UFSP2 Eleanor Williams Source Expert Review Green was added to UFSP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 SGMS2 Eleanor Williams Source Expert Review Green was added to SGMS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 SCUBE3 Eleanor Williams Source Expert Review Green was added to SCUBE3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 MYO18B Eleanor Williams Source Expert Review Green was added to MYO18B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 MESD Eleanor Williams Source Expert Review Green was added to MESD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 LTBP1 Eleanor Williams Source Expert Review Green was added to LTBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 LRRK1 Eleanor Williams Source Expert Review Green was added to LRRK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 FBN2 Eleanor Williams Mode of inheritance for gene FBN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.183 DSPP Eleanor Williams Source Expert Review Red was added to DSPP.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Skeletal dysplasia v2.183 DLX5 Eleanor Williams Mode of inheritance for gene DLX5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.183 COPB2 Eleanor Williams Source Expert Review Green was added to COPB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.183 ARCN1 Eleanor Williams Source Expert Review Green was added to ARCN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.182 TBXAS1 Eleanor Williams Phenotypes for gene: TBXAS1 were changed from Ghosal hematodiaphyseal syndrome 231095 to Ghosal hematodiaphyseal syndrome, OMIM:231095
Skeletal dysplasia v2.181 TBXAS1 Eleanor Williams Tag for-review was removed from gene: TBXAS1.
Skeletal dysplasia v2.181 TBXAS1 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated followingNHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.181 KIAA1217 Eleanor Williams Tag for-review was removed from gene: KIAA1217.
Skeletal dysplasia v2.181 HS2ST1 Eleanor Williams Phenotypes for gene: HS2ST1 were changed from Intellectual disability; dysmorphic features; congenital anomalies to Intellectual disability; dysmorphic features; congenital anomalies; Neurofacioskeletal syndrome with or without renal agenesis,OMIM:619194
Skeletal dysplasia v2.180 HS2ST1 Eleanor Williams Tag for-review was removed from gene: HS2ST1.
Skeletal dysplasia v2.180 GZF1 Eleanor Williams Tag for-review was removed from gene: GZF1.
Skeletal dysplasia v2.180 PRKG2 Eleanor Williams Tag for-review was removed from gene: PRKG2.
Skeletal dysplasia v2.180 MTX2 Eleanor Williams Phenotypes for gene: MTX2 were changed from Skeletal dysplasia; Mandibuloacral dysplasia; lipodystrophy; arterial calcification to Skeletal dysplasia; Mandibuloacral dysplasia; lipodystrophy; arterial calcification; Mandibuloacral dysplasia progeroid syndrome, OMIM:619127
Skeletal dysplasia v2.179 MTX2 Eleanor Williams Tag for-review was removed from gene: MTX2.
Skeletal dysplasia v2.179 KDELR2 Eleanor Williams Tag for-review was removed from gene: KDELR2.
Skeletal dysplasia v2.179 PISD Eleanor Williams Phenotypes for gene: PISD were changed from Liberfarb syndrome, 618889 to Liberfarb syndrome, OMIM:618889
Skeletal dysplasia v2.178 PISD Eleanor Williams Tag for-review was removed from gene: PISD.
Skeletal dysplasia v2.178 TONSL Eleanor Williams Tag for-review was removed from gene: TONSL.
Skeletal dysplasia v2.178 NXN Eleanor Williams Phenotypes for gene: NXN were changed from Robinow syndrome, autosomal recessive 2 618529 to Robinow syndrome, autosomal recessive 2, OMIM:618529
Skeletal dysplasia v2.177 NXN Eleanor Williams Tag for-review was removed from gene: NXN.
Skeletal dysplasia v2.177 CSGALNACT1 Eleanor Williams Tag for-review was removed from gene: CSGALNACT1.
Skeletal dysplasia v2.177 COG4 Eleanor Williams Tag for-review was removed from gene: COG4.
Skeletal dysplasia v2.177 NPR3 Eleanor Williams Tag for-review was removed from gene: NPR3.
Skeletal dysplasia v2.177 SMAD6 Eleanor Williams Phenotypes for gene: SMAD6 were changed from Radioulnar synostosis to {Radioulnar synostosis, nonsyndromic}, OMIM:179300
Skeletal dysplasia v2.176 SMAD6 Eleanor Williams Tag for-review was removed from gene: SMAD6.
Skeletal dysplasia v2.176 RINT1 Eleanor Williams Tag for-review was removed from gene: RINT1.
Skeletal dysplasia v2.176 MBTPS1 Eleanor Williams Tag for-review was removed from gene: MBTPS1.
Skeletal dysplasia v2.176 POLR1B Eleanor Williams Tag for-review was removed from gene: POLR1B.
Skeletal dysplasia v2.176 PKDCC Eleanor Williams Tag for-review was removed from gene: PKDCC.
Skeletal dysplasia v2.176 HS2ST1 Eleanor Williams commented on gene: HS2ST1
Skeletal dysplasia v2.176 TBXAS1 Eleanor Williams commented on gene: TBXAS1: The mode of inheritance of this gene has been updated followingNHS Genomic Medicine Service approval.
Skeletal dysplasia v2.176 KIAA1217 Eleanor Williams commented on gene: KIAA1217: The rating of this gene has been updated following NHS Genomic Medicine Service approval. It has been demoted to red as per reviewer recommendation.
Skeletal dysplasia v2.176 GZF1 Eleanor Williams commented on gene: GZF1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.176 PRKG2 Eleanor Williams commented on gene: PRKG2
Skeletal dysplasia v2.176 MTX2 Eleanor Williams commented on gene: MTX2
Skeletal dysplasia v2.176 KDELR2 Eleanor Williams commented on gene: KDELR2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.176 PISD Eleanor Williams commented on gene: PISD
Skeletal dysplasia v2.176 TONSL Eleanor Williams commented on gene: TONSL: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.176 NXN Eleanor Williams commented on gene: NXN
Skeletal dysplasia v2.176 CSGALNACT1 Eleanor Williams commented on gene: CSGALNACT1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.176 COG4 Eleanor Williams commented on gene: COG4
Skeletal dysplasia v2.176 NPR3 Eleanor Williams commented on gene: NPR3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.176 SMAD6 Eleanor Williams commented on gene: SMAD6
Skeletal dysplasia v2.176 RINT1 Eleanor Williams commented on gene: RINT1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.176 MBTPS1 Eleanor Williams commented on gene: MBTPS1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.176 POLR1B Eleanor Williams commented on gene: POLR1B: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.176 PKDCC Eleanor Williams commented on gene: PKDCC: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.175 TBXAS1 Eleanor Williams Mode of inheritance for gene TBXAS1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.175 KIAA1217 Eleanor Williams Source Expert Review Red was added to KIAA1217.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Skeletal dysplasia v2.175 HS2ST1 Eleanor Williams Source Expert Review Green was added to HS2ST1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 GZF1 Eleanor Williams Source Expert Review Green was added to GZF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 PRKG2 Eleanor Williams Source Expert Review Green was added to PRKG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 MTX2 Eleanor Williams Source Expert Review Green was added to MTX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 KDELR2 Eleanor Williams Source Expert Review Green was added to KDELR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 PISD Eleanor Williams Source Expert Review Green was added to PISD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 TONSL Eleanor Williams Source Expert Review Green was added to TONSL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 NXN Eleanor Williams Source Expert Review Green was added to NXN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 CSGALNACT1 Eleanor Williams Source Expert Review Green was added to CSGALNACT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 COG4 Eleanor Williams Source Expert Review Green was added to COG4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 NPR3 Eleanor Williams Source Expert Review Green was added to NPR3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 SMAD6 Eleanor Williams Source Expert Review Green was added to SMAD6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 RINT1 Eleanor Williams Source Expert Review Green was added to RINT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 MBTPS1 Eleanor Williams Source Expert Review Green was added to MBTPS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 POLR1B Eleanor Williams Source Expert Review Green was added to POLR1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.175 PKDCC Eleanor Williams Source Expert Review Green was added to PKDCC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.174 LTBP3 Eleanor Williams Phenotypes for gene: LTBP3 were changed from Geleophysic dysplasia 3 617809; Dental anomalies and short stature 610216; Geleophysic dysplasia 3 617809 to Geleophysic dysplasia 3, OMIM:617809; Dental anomalies and short stature, OMIM:610216; geleophysic dysplasia 3, MONDO:0054722,
Skeletal dysplasia v2.173 LTBP3 Eleanor Williams Publications for gene: LTBP3 were set to 27068007
Skeletal dysplasia v2.172 LTBP3 Eleanor Williams Added comment: Comment on mode of inheritance: The mode of inheritance should be updated to Both mono- and bi-allelic at the next GMS review.
Skeletal dysplasia v2.172 LTBP3 Eleanor Williams Mode of inheritance for gene: LTBP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.171 LTBP3 Eleanor Williams Tag Q1_22_NHS_review tag was added to gene: LTBP3.
Tag Q1_22_MOI tag was added to gene: LTBP3.
Skeletal dysplasia v2.171 LTBP3 Eleanor Williams changed review comment from: This gene originally had the mode of inheritance set to monoallelic based on the Geleophysic dysplasia 3 OMIM:617809 phenotype.

As Tracy Lester reports there are more than cases of patients with both a dental phenotype and short stature and so the mode of inheritance should be updated to both mono- and bi-allelic.

PMID: 25899461 - Dugan et al 2015 - 2 sisters with homozygous truncating mutations (1 bp insertion) in LTBP3. Only this gene was analysed. They presented with oligodontia, short stature and mitral valve prolapse.

PMID: 25669657 - Huckert et al 2015 - report 4 families (3 consanguineous) with a phenotype of significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta. WES identified homozygous or compound het protein altering variants in LTBP3 in all patients (14 bp deletion, nonsense variant, splice site variant, 2 1bp deletions).

PMID:19344874 - Noor et al 2009 - consanguineous Pakistani family with oligodontia along with short stature in an autosomal-recessive fashion. A homozygous nonsense mutation, Y774X, within LTBP3 was identified.

PMID: 8721563 (abstract only accessed) and PMID: 19213025 report patients with a dental and skeletal phenotype but no genetic analysis.; to: This gene originally had the mode of inheritance set to monoallelic based on the Geleophysic dysplasia 3 OMIM:617809 phenotype. This is supported by heterozygous variants in LTBP3 reported in PMID: 27068007 (McInerney-Leo et al 2016) - 2 cases with geleophysic dysplasia and 1 with acromelic dysplasia and PMID: 33082559 (Marzin et al 2021) - 2 cases with geleophysic dysplasia and 1 with acromelic dysplasia . Dental anomalies are not reported in either set of cases.

As Tracy Lester reports there are more than 3 cases of patients with both a dental phenotype and short stature and so the mode of inheritance should be updated to both mono- and bi-allelic.

PMID: 25899461 - Dugan et al 2015 - 2 sisters with homozygous truncating mutations (1 bp insertion) in LTBP3. Only this gene was analysed. They presented with oligodontia, short stature and mitral valve prolapse.

PMID: 25669657 - Huckert et al 2015 - report 4 families (3 consanguineous) with a phenotype of significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta. WES identified homozygous or compound het protein altering variants in LTBP3 in all patients (14 bp deletion, nonsense variant, splice site variant, 2 1bp deletions).

PMID:19344874 - Noor et al 2009 - consanguineous Pakistani family with oligodontia along with short stature in an autosomal-recessive fashion. A homozygous nonsense mutation, Y774X, within LTBP3 was identified.

PMID: 8721563 (abstract only accessed) and PMID: 19213025 report patients with a dental and skeletal phenotype but no genetic analysis.
Skeletal dysplasia v2.171 LTBP3 Eleanor Williams edited their review of gene: LTBP3: Added comment: This gene originally had the mode of inheritance set to monoallelic based on the Geleophysic dysplasia 3 OMIM:617809 phenotype.

As Tracy Lester reports there are more than cases of patients with both a dental phenotype and short stature and so the mode of inheritance should be updated to both mono- and bi-allelic.

PMID: 25899461 - Dugan et al 2015 - 2 sisters with homozygous truncating mutations (1 bp insertion) in LTBP3. Only this gene was analysed. They presented with oligodontia, short stature and mitral valve prolapse.

PMID: 25669657 - Huckert et al 2015 - report 4 families (3 consanguineous) with a phenotype of significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta. WES identified homozygous or compound het protein altering variants in LTBP3 in all patients (14 bp deletion, nonsense variant, splice site variant, 2 1bp deletions).

PMID:19344874 - Noor et al 2009 - consanguineous Pakistani family with oligodontia along with short stature in an autosomal-recessive fashion. A homozygous nonsense mutation, Y774X, within LTBP3 was identified.

PMID: 8721563 (abstract only accessed) and PMID: 19213025 report patients with a dental and skeletal phenotype but no genetic analysis.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.171 LIFR Eleanor Williams changed review comment from: Comment on mode of inheritance: Mode of inheritance of BIALLELIC is correct for the Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome phenotype and this panel. Heterozygous variants and a CAKUT phenotype.; to: Comment on mode of inheritance: Mode of inheritance of BIALLELIC is correct for the Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome phenotype and this panel. Heterozygous variants are associated with a CAKUT phenotype.
Skeletal dysplasia v2.171 LIFR Eleanor Williams Added comment: Comment on mode of inheritance: Mode of inheritance of BIALLELIC is correct for the Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome phenotype and this panel. Heterozygous variants and a CAKUT phenotype.
Skeletal dysplasia v2.171 LIFR Eleanor Williams Mode of inheritance for gene: LIFR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.170 LTBP3 Tracy Lester edited their review of gene: LTBP3: Added comment: Dental anomalies with short stature is recessive. Several cases reported - pathogenic variant almost missed because gene was tiered under AD mode of inheritance only.; Changed publications to: 19213025, 25899461, 25669657, 19344874, 8721563; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Set current diagnostic: yes
Skeletal dysplasia v2.170 ANAPC1 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: ANAPC1.
Skeletal dysplasia v2.170 TNFRSF11A Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: TNFRSF11A.
Skeletal dysplasia v2.170 CSNK1G1 Sarah Leigh Classified gene: CSNK1G1 as Amber List (moderate evidence)
Skeletal dysplasia v2.170 CSNK1G1 Sarah Leigh Gene: csnk1g1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.169 CSNK1G1 Sarah Leigh gene: CSNK1G1 was added
gene: CSNK1G1 was added to Skeletal dysplasia. Sources: NHS GMS
Q1_22_rating tags were added to gene: CSNK1G1.
Mode of inheritance for gene: CSNK1G1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CSNK1G1 were set to 24463883; 33009664
Phenotypes for gene: CSNK1G1 were set to early-onset epileptic encephalopathy and microcephaly
Review for gene: CSNK1G1 was set to AMBER
Added comment: Not associated with relevant phenotype in OMIM and as limited evidence on Gen2Phen for association with early-onset epileptic encephalopathy and microcephaly.
NHS Genomic Medicine Service review of CSNK1G1 on the Intellectual disability panel, recommended that CSNK1G1 should be made amber / green on the skeletal dysplasia panel; as skeletal features were reported in 2/5 reported cases (PMID: 33009664)TL.
Sources: NHS GMS
Skeletal dysplasia v2.168 GPX4 Zornitza Stark changed review comment from: PMID: 32827718
1x consaguineous family with 2x infants who died within first week of life. Homozygous frameshift variant.; to: PMID: 32827718
New consaguineous family with 2x infants who died within first week of life. Homozygous frameshift variant.
Skeletal dysplasia v2.168 GPX4 Zornitza Stark reviewed gene: GPX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24706940, 32827718; Phenotypes: Spondylometaphyseal dysplasia, Sedaghatian type MIM#250220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.168 BMP2 Jenny Simmonds reviewed gene: BMP2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 21357617, 29129813, 24710560, 19327734; Phenotypes: Brachydactyly, type A2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.168 DSPP Michael Oldridge changed review comment from: agree should be demoted to Red.
Dentinogenesis imperfecta appears to only affect the teeth, no evidence of OI phenotype in these cases.; to: agree should be demoted to Red.
Dentinogenesis imperfecta appears to only affect the teeth, no evidence of OI phenotype in reported cases.
Skeletal dysplasia v2.168 DSPP Michael Oldridge reviewed gene: DSPP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dentinogenesis imperfecta; Mode of inheritance: None
Skeletal dysplasia v2.168 PDIA6 Eleanor Williams commented on gene: PDIA6: Added this gene to this panel on advice from Genomics England clinical team. Rating amber as 1 case plus functional data.
Skeletal dysplasia v2.168 PDIA6 Eleanor Williams Entity copied from Skeletal ciliopathies v1.15
Skeletal dysplasia v2.168 PDIA6 Eleanor Williams gene: PDIA6 was added
gene: PDIA6 was added to Skeletal dysplasia. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: PDIA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDIA6 were set to 33495992
Phenotypes for gene: PDIA6 were set to Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes
Skeletal dysplasia v2.167 SH3BP2 Arina Puzriakova Phenotypes for gene: SH3BP2 were changed from Cherubism 118400 to Cherubism, OMIM:118400
Skeletal dysplasia v2.166 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from Chronic infantile neurologic cutaneous articular syndrome (CINA) - 607115; CINCA (Infantile-onset multisystem inflammatory disease) 607115 to CINCA syndrome, OMIM:607115
Skeletal dysplasia v2.165 LPIN2 Arina Puzriakova Phenotypes for gene: LPIN2 were changed from Majeed syndrome (Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia) 609628 to Majeed syndrome, OMIM:609628; Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia
Skeletal dysplasia v2.164 IL1RN Arina Puzriakova Phenotypes for gene: IL1RN were changed from Interleukin 1 receptor antagonist deficiency 612852; Interleukin 1 receptor antagonist deficiency 612852 to Interleukin 1 receptor antagonist deficiency, OMIM:612852
Skeletal dysplasia v2.163 PRKG2 Arina Puzriakova Added comment: Comment on phenotypes: Added relevant phenotypes now listed in OMIM (MIM# 619636 and MIM# 619638)
Skeletal dysplasia v2.163 PRKG2 Arina Puzriakova Phenotypes for gene: PRKG2 were changed from acromesomelic dysplasia, MONDO:0019696; spondylometaphyseal dysplasia, MONDO:0016763 to Acromesomelic dysplasia 4, OMIM:619636; Spondylometaphyseal dysplasia, Pagnamenta type, OMIM:619638
Skeletal dysplasia v2.162 HHAT Eleanor Williams Classified gene: HHAT as Amber List (moderate evidence)
Skeletal dysplasia v2.162 HHAT Eleanor Williams Added comment: Comment on list classification: Promotion from grey to amber but with a recommendation for green rating following GMS review. 3 cases reported with a skeletal dysplasia phenotype and variants in HHAT.
Skeletal dysplasia v2.162 HHAT Eleanor Williams Gene: hhat has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.161 HHAT Eleanor Williams Tag Q4_21_rating tag was added to gene: HHAT.
Skeletal dysplasia v2.161 HHAT Eleanor Williams changed review comment from: Associated with Nivelon-Nivelon-Mabille syndrome #600092 (AR) in OMIM.

PMID:24784881 - Callier et al 2014 - report a family with 2 siblings with Disorder of Sex Development (DSD) and chondrodysplasia (Nivelon-Nivelon-Mabille syndrome). The first sibling (46,XY karyotype) displayed severe dwarfism with generalized chondrodysplasia, a narrow, bell-shaped thorax, micromelia, brachydactyly, severe microcephaly (-7.5 SD at age 16 (PMID:15578577) with cerebellar vermis hypoplasia, facial anomalies, hypoplastic irides, and coloboma of both optic discs. Complete gonadal dysgenesis and intellectual disability is also noted. The second sibling (46,XX karyotype) had histologically normal ovaries and similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia. Using WES a homozygous missense variant was found NM_001122834:c.860G>T:p.(Gly287Val) in HHAT in the first sibling which is in the conserved MBOAT domain. The parents were heterozygous.

PMID:30912300 - Abdel-Salam et al 2019 - report two siblings with progressive microcephaly (-6 SD at age 6 and age 3 for the 2 siblings respectively), early infantile onset seizures, and cerebellar vermis hypoplasia but notably without dwarfism and gonadal dysgenesis. Skeletal x-rays of both siblings showed nlarged epiphyses and metaphyses, thinning of the lateral 1/3 of clavicles and trapezoidal vertebral bodies. WES found a homozygous missense (c.770T>C, p.[Leu257Pro]) HHAT which is in the conserved MBOAT domain. Both parents were heterozygous for the variant.

PMID: 33749989 - Pande et al 2021 - report multiple malformations in three pregnancies with a novel biallelic in-frame deletion, c.365_367del; (p.Thr122del), in exon 5 of HHAT in the living proband. She shows severe microphthalmia, microcephaly (−8 SD head circumference at age 7), skeletal dysplasia (narrow bell-shaped tho-rax, short and angel-shaped epiphyses of hands and feet) and midfac eretrusion, short columella with a groove at the base, prominent ears, long philtrum, depressed nasal bridge, everted lower lip, and a singlec entral incisor. She also has complete sex reversal (karyotype of 46, XY, normal internal organs including uterus and ovaries.); to: Associated with Nivelon-Nivelon-Mabille syndrome #600092 (AR) in OMIM.

PMID:24784881 - Callier et al 2014 - report a family with 2 siblings with Disorder of Sex Development (DSD) and chondrodysplasia (Nivelon-Nivelon-Mabille syndrome). The first sibling (46,XY karyotype) displayed severe dwarfism with generalized chondrodysplasia, a narrow, bell-shaped thorax, micromelia, brachydactyly, severe microcephaly (-7.5 SD at age 16 (PMID:15578577) with cerebellar vermis hypoplasia, facial anomalies, hypoplastic irides, and coloboma of both optic discs. Complete gonadal dysgenesis ( including normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) and intellectual disability is also noted. The second sibling (46,XX karyotype) had histologically normal ovaries and similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia. Using WES a homozygous missense variant was found NM_001122834:c.860G>T:p.(Gly287Val) in HHAT in the first sibling which is in the conserved MBOAT domain. The parents were heterozygous. They also found that mice lacking functional Hhat show a similar phenotype as the syndromic 46,XY DSD patient including testicular dysgenesis and skeletal defects.

PMID:30912300 - Abdel-Salam et al 2019 - report two siblings with progressive microcephaly (-6 SD at age 6 and age 3 for the 2 siblings respectively), early infantile onset seizures, and cerebellar vermis hypoplasia but notably without dwarfism and gonadal dysgenesis. Skeletal x-rays of both siblings showed enlarged epiphyses and metaphyses, thinning of the lateral 1/3 of clavicles and trapezoidal vertebral bodies. Both sisters had a normal female karyotype (46, XX). WES found a homozygous missense (c.770T>C, p.[Leu257Pro]) HHAT which is in the conserved MBOAT domain. Both parents were heterozygous for the variant.

PMID: 33749989 - Pande et al 2021 - report multiple malformations in three pregnancies with a novel biallelic in-frame deletion, c.365_367del; (p.Thr122del), in exon 5 of HHAT in the living proband. She shows severe microphthalmia, microcephaly (−8 SD head circumference at age 7), skeletal dysplasia (narrow bell-shaped tho-rax, short and angel-shaped epiphyses of hands and feet) and midfac eretrusion, short columella with a groove at the base, prominent ears, long philtrum, depressed nasal bridge, everted lower lip, and a singlec entral incisor. She also has complete sex reversal (karyotype of 46, XY, normal internal organs including uterus and ovaries.)
Skeletal dysplasia v2.161 HHAT Eleanor Williams Phenotypes for gene: HHAT were changed from Nivelon-Nivelon-Mabille syndrome 600092 to Nivelon-Nivelon-Mabille syndrome, OMIM:600092
Skeletal dysplasia v2.160 HHAT Eleanor Williams Publications for gene: HHAT were set to 24784881; 30912300
Skeletal dysplasia v2.159 HHAT Eleanor Williams reviewed gene: HHAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 24784881, 30912300, 33749989; Phenotypes: Nivelon-Nivelon-Mabille syndrome, OMIM:600092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.159 MESD Eleanor Williams Tag Q3_21_NHS_review tag was added to gene: MESD.
Skeletal dysplasia v2.159 PRKG2 Eleanor Williams Tag Q4_21_NHS_review tag was added to gene: PRKG2.
Skeletal dysplasia v2.159 ZNF687 Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: ZNF687.
Skeletal dysplasia v2.159 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from Martsolf syndrome to Martsolf syndrome 1, OMIM:212720
Skeletal dysplasia v2.158 RAB3GAP2 Arina Puzriakova Mode of inheritance for gene: RAB3GAP2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.157 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Singleton-Merten syndrome 1, 182250 to Singleton-Merten syndrome 1, OMIM:182250
Skeletal dysplasia v2.156 PRKG2 Eleanor Williams Phenotypes for gene: PRKG2 were changed from Acromesomelic dysplasia to acromesomelic dysplasia, MONDO:0019696; spondylometaphyseal dysplasia, MONDO:0016763
Skeletal dysplasia v2.155 PRKG2 Eleanor Williams Publications for gene: PRKG2 were set to 33106379
Skeletal dysplasia v2.154 PRKG2 Alistair Pagnamenta reviewed gene: PRKG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34782440, 33106379, 34680883; Phenotypes: spondylometaphyseal, acromesomelic dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.154 ZNF687 Eleanor Williams Phenotypes for gene: ZNF687 were changed from Paget Disease of Bone with associated Giant Cell Tumour. to Paget disease of bone 6, OMIM:616833
Skeletal dysplasia v2.153 ZNF687 Eleanor Williams Publications for gene: ZNF687 were set to PMID: 29493781, PMID: 28968976, PMID: 26849110
Skeletal dysplasia v2.152 ZNF687 Eleanor Williams Classified gene: ZNF687 as Amber List (moderate evidence)
Skeletal dysplasia v2.152 ZNF687 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber but with a recommendation for a green rating following GMS review.
Skeletal dysplasia v2.152 ZNF687 Eleanor Williams Gene: znf687 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.151 ZNF687 Eleanor Williams Tag Q4_21_rating tag was added to gene: ZNF687.
Skeletal dysplasia v2.151 ZNF687 Eleanor Williams reviewed gene: ZNF687: Rating: GREEN; Mode of pathogenicity: None; Publications: 29493781, 26849110; Phenotypes: Paget disease of bone 6, OMIM:616833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.151 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Skeletal dysplasia v2.150 ATXN10 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: ATXN10.
Skeletal dysplasia v2.150 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Skeletal dysplasia v2.150 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from to Other
Skeletal dysplasia v2.149 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from to Spinocerebellar ataxia 10, OMIM:603516
Skeletal dysplasia v2.148 SHOX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SHOX.
Skeletal dysplasia v2.148 SMARCE1 Arina Puzriakova Mode of inheritance for gene: SMARCE1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.147 SMARCE1 Arina Puzriakova Phenotypes for gene: SMARCE1 were changed from Coffin-Siris syndrome to Coffin-Siris syndrome 5, OMIM:616938
Skeletal dysplasia v2.146 EXTL3 Arina Puzriakova Phenotypes for gene: EXTL3 were changed from Immunoskeletal dysplasia with neurodevelopmental abnormalities 617425; Immunoskeletal dysplasia with neurodevelopmental abnormalities 617425 to Immunoskeletal dysplasia with neurodevelopmental abnormalities, OMIM:617425
Skeletal dysplasia v2.145 COL9A3 Arina Puzriakova Phenotypes for gene: COL9A3 were changed from MED; multiple epiphyseal dysplasia; Epiphyseal dysplasia, multiple, with myopathy; Stickler syndrome type VI; multiple epiphyseal dysplasia 3, with or without myopathy - 600969; Multiple Epiphyseal Dysplasia, Dominant; Mutiple Epiphyseal Dysplasia to Epiphyseal dysplasia, multiple, 3, with or without myopathy, OMIM:600969
Skeletal dysplasia v2.144 COL9A2 Arina Puzriakova Phenotypes for gene: COL9A2 were changed from Epiphyseal dysplasia, multiple, 2 600204; Stickler syndrome, type V 614284; Stickler syndrome, type V, 614284; {Intervertebral disc disease, susceptibility to}, 603932 to Stickler syndrome, type V, OMIM:614284; Epiphyseal dysplasia, multiple, 2, OMIM:600204
Skeletal dysplasia v2.143 COL9A1 Arina Puzriakova Tag Q4_21_MOI tag was added to gene: COL9A1.
Skeletal dysplasia v2.143 COL9A1 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Monoallelic' to 'Both mono- and biallelic' at the next GMS panel update. COL9A1 is associated with two relevant disorders as they both include epiphyseal dysplasia - one of which shows biallelic inheritance (Stickler syndrome, type IV, OMIM:614134) while the other is associated with monoallelic inheritance (Epiphyseal dysplasia, multiple, 6, OMIM:614135)
Skeletal dysplasia v2.143 COL9A1 Arina Puzriakova Mode of inheritance for gene: COL9A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.142 COL9A1 Arina Puzriakova Phenotypes for gene: COL9A1 were changed from Stickler syndrome, type IV 614134; Epiphyseal dysplasia, multiple, 6 614135 to Stickler syndrome, type IV, OMIM:614134; Epiphyseal dysplasia, multiple, 6, OMIM:614135
Skeletal dysplasia v2.141 ZNF687 Adrienne Flanagan gene: ZNF687 was added
gene: ZNF687 was added to Skeletal dysplasia. Sources: Other,Research
Mode of inheritance for gene: ZNF687 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF687 were set to PMID: 29493781, PMID: 28968976, PMID: 26849110
Phenotypes for gene: ZNF687 were set to Paget Disease of Bone with associated Giant Cell Tumour.
Penetrance for gene: ZNF687 were set to unknown
Mode of pathogenicity for gene: ZNF687 was set to Other
Review for gene: ZNF687 was set to GREEN
Added comment: Missense mutation c.2810C>G (p.Pro937Arg) alters the nuclear-ctyoplasmic balance of ZNF687 by generating a stronger nuclear localisation signal thereby acting as a gain-of-function mutation.
Sources: Other, Research
Skeletal dysplasia v2.141 COL11A1 Arina Puzriakova Phenotypes for gene: COL11A1 were changed from Stickler syndrome, type II 604841; Marshall syndrome 154780; Fibrochondrogenesis 1 228520 to Stickler syndrome, type II, OMIM:604841; Marshall syndrome, OMIM:154780; Fibrochondrogenesis 1, OMIM:228520
Skeletal dysplasia v2.140 CLCN7 Arina Puzriakova Phenotypes for gene: CLCN7 were changed from Osteopetrosis, autosomal recessive 4 611490; Osteopetrosis, autosomal dominant 2 166600 to Osteopetrosis, autosomal recessive 4, OMIM:611490; Osteopetrosis, autosomal dominant 2, OMIM:166600
Skeletal dysplasia v2.139 TMEM251 Eleanor Williams Classified gene: TMEM251 as Amber List (moderate evidence)
Skeletal dysplasia v2.139 TMEM251 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. 2 cases reported.
Skeletal dysplasia v2.139 TMEM251 Eleanor Williams Gene: tmem251 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.138 TMEM251 Eleanor Williams Phenotypes for gene: TMEM251 were changed from Dysostosis multiplex‐like skeletal dysplasia; severe short stature to Dysostosis multiplex, Ain-Naz type, OMIM:19345; severe short stature
Skeletal dysplasia v2.137 TMEM251 Eleanor Williams reviewed gene: TMEM251: Rating: AMBER; Mode of pathogenicity: None; Publications: 33252156; Phenotypes: Dysostosis multiplex, Ain-Naz type, OMIM:19345; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.137 SCUBE3 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 5 variants reported in 5 unrelated cases, together with supportive functional and mouse model studies (PMID 33308444).; to: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. PMID 33308444 reports eight SCUBE variants in nine unrelated families, including eighteen affected members. In vtro studies demonstrated a variable impact of disease-causing variants on transcript processing, protein secretion and function, resulting in dysregulation on bone morphogenetic protein (BMP) signaling and a Scube3−/− mouse showed shared phenotypic features with OMIM:619184.
Skeletal dysplasia v2.137 SCUBE3 Sarah Leigh Phenotypes for gene: SCUBE3 were changed from Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies OMIM:619184 to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies OMIM:619184; short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2 MONDO:0030953
Skeletal dysplasia v2.136 BMP2 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the mode of inheritance as monoallelic. OMIM also reports the biallelic phenotype of {HFE hemochromatosis, modifier of} but this is not relevant to this panel.
Skeletal dysplasia v2.136 BMP2 Eleanor Williams Mode of inheritance for gene: BMP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.135 SLC29A3 Arina Puzriakova Phenotypes for gene: SLC29A3 were changed from Histiocytosis-lymphadenopathy plus syndrome 602782 to Histiocytosis-lymphadenopathy plus syndrome, OMIM:602782
Skeletal dysplasia v2.134 MYO18B Arina Puzriakova Classified gene: MYO18B as Amber List (moderate evidence)
Skeletal dysplasia v2.134 MYO18B Arina Puzriakova Added comment: Comment on list classification: There are sufficient unrelated cases presenting with a relevant phenotype associated with variants in this gene to rate as Green at the next GMS panel update.
Skeletal dysplasia v2.134 MYO18B Arina Puzriakova Gene: myo18b has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.133 MYO18B Arina Puzriakova Publications for gene: MYO18B were set to PMID: 32637634
Skeletal dysplasia v2.132 MYO18B Arina Puzriakova Tag Q3_21_rating tag was added to gene: MYO18B.
Skeletal dysplasia v2.132 MYO18B Arina Puzriakova reviewed gene: MYO18B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25748484, 31195167, 32184166, 32637634, 33179433; Phenotypes: Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, OMIM:616549; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.132 MYO18B Arina Puzriakova Phenotypes for gene: MYO18B were changed from Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, OMIM:616549
Skeletal dysplasia v2.131 ARCN1 Arina Puzriakova Tag Q3_21_rating tag was added to gene: ARCN1.
Skeletal dysplasia v2.131 ARCN1 Arina Puzriakova Publications for gene: ARCN1 were set to PMID: 27476655
Skeletal dysplasia v2.130 ARCN1 Arina Puzriakova Classified gene: ARCN1 as Amber List (moderate evidence)
Skeletal dysplasia v2.130 ARCN1 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Andžela Lazdāne. ARCN1 is associated with a relevant phenotype in OMIM (MIM# 617164) which is characterised by rhizomelic short stature. At least 6 individuals from 5 unrelated families reported in literature (PMIDs: 27476655; 31075182; 33154040), which is sufficient to rate this gene as Green at the next GMS panel update.
Skeletal dysplasia v2.130 ARCN1 Arina Puzriakova Gene: arcn1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.129 ARCN1 Arina Puzriakova Phenotypes for gene: ARCN1 were changed from Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay to Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay, OMIM:617164
Skeletal dysplasia v2.128 LRRK1 Eleanor Williams Classified gene: LRRK1 as Amber List (moderate evidence)
Skeletal dysplasia v2.128 LRRK1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, but with a recommendation for a green rating following GMS review. More than 3 reported cases.
Skeletal dysplasia v2.128 LRRK1 Eleanor Williams Gene: lrrk1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.127 LRRK1 Eleanor Williams Tag Q3_21_rating tag was added to gene: LRRK1.
Tag Q3_21_NHS_review tag was added to gene: LRRK1.
Skeletal dysplasia v2.127 LRRK1 Eleanor Williams commented on gene: LRRK1
Skeletal dysplasia v2.127 LRRK1 Eleanor Williams Phenotypes for gene: LRRK1 were changed from Osteosclerotic metaphyseal dysplasia (OSMD) (OMIM: 615198) to Osteosclerotic metaphyseal dysplasia (OSMD), OMIM: 615198; Osteosclerotic metaphyseal dysplasia, MONDO:0014080
Skeletal dysplasia v2.126 UNC45A Eleanor Williams commented on gene: UNC45A: Copied this gene from the Osteogenesis imperfecta panel, as all green genes on that panel should also be green on the Skeletal dysplasia panel
Skeletal dysplasia v2.126 UNC45A Eleanor Williams Entity copied from Osteogenesis imperfecta v2.37
Skeletal dysplasia v2.126 UNC45A Eleanor Williams gene: UNC45A was added
gene: UNC45A was added to Skeletal dysplasia. Sources: Expert list,Expert Review Amber
Q3_21_rating, Q3_21_NHS_review tags were added to gene: UNC45A.
Mode of inheritance for gene: UNC45A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC45A were set to 29429573
Phenotypes for gene: UNC45A were set to Osteootohepatoenteric syndrome, OMIM:619377
Skeletal dysplasia v2.125 SGMS2 Eleanor Williams commented on gene: SGMS2: Copied from the Osteogenesis imperfecta panel to the Skeletal dysplasia panel.
Skeletal dysplasia v2.125 SGMS2 Eleanor Williams Entity copied from Osteogenesis imperfecta v2.37
Skeletal dysplasia v2.125 SGMS2 Eleanor Williams gene: SGMS2 was added
gene: SGMS2 was added to Skeletal dysplasia. Sources: Expert list,Expert Review Amber
Q3_21_rating tags were added to gene: SGMS2.
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia, OMIM:126550; calvarial doughnut lesions-bone fragility syndrome, MONDO:0007470
Skeletal dysplasia v2.124 DSPP Eleanor Williams Tag Q3_21_expert_review tag was added to gene: DSPP.
Skeletal dysplasia v2.124 DSPP Eleanor Williams commented on gene: DSPP: This gene has been reviewed as RED on the Osteogenesis imperfecta panel by Zorntiza Stark with comment "Specifically NOT associated with fractures/OI.", and therefore has been tagged for further GMS review on this panel also.
Skeletal dysplasia v2.124 MESD Eleanor Williams Tag for-review was removed from gene: MESD.
Tag Q3_21_rating tag was added to gene: MESD.
Skeletal dysplasia v2.124 MESD Eleanor Williams Entity copied from Osteogenesis imperfecta v2.37
Skeletal dysplasia v2.124 MESD Eleanor Williams gene: MESD was added
gene: MESD was added to Skeletal dysplasia. Sources: Expert Review Amber,Literature
for-review tags were added to gene: MESD.
Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MESD were set to 31564437
Phenotypes for gene: MESD were set to Osteogenesis imperfecta, type XX, OMIM:618644; Osteogenesis imperfecta, type 20, MONDO:0032846
Skeletal dysplasia v2.123 MBTPS2 Eleanor Williams commented on gene: MBTPS2: Copied from the Osteogenesis imperfecta panel
Skeletal dysplasia v2.123 MBTPS2 Eleanor Williams Entity copied from Osteogenesis imperfecta v2.37
Skeletal dysplasia v2.123 MBTPS2 Eleanor Williams gene: MBTPS2 was added
gene: MBTPS2 was added to Skeletal dysplasia. Sources: Expert list,Expert Review Amber
Q3_21_rating, Q3_21_expert_review tags were added to gene: MBTPS2.
Mode of inheritance for gene: MBTPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MBTPS2 were set to 27380894
Phenotypes for gene: MBTPS2 were set to Osteogenesis imperfecta, type XIX, OMIM:301014; osteogenesis imperfecta, type 19, MONDO:0049223
Skeletal dysplasia v2.122 SUCO Eleanor Williams commented on gene: SUCO: Copied from the Osteogenesis imperfecta panel to the Skeletal Dysplasia panel. Amber rating.
Skeletal dysplasia v2.122 SUCO Eleanor Williams Entity copied from Osteogenesis imperfecta v2.37
Skeletal dysplasia v2.122 SUCO Eleanor Williams gene: SUCO was added
gene: SUCO was added to Skeletal dysplasia. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SUCO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUCO were set to 29620724; 20440000
Phenotypes for gene: SUCO were set to Osteogenesis imperfecta, MONDO:0019019; skeletal dysplasia, HP:0002652; osteopenia
Skeletal dysplasia v2.121 COPB2 Eleanor Williams Classified gene: COPB2 as Amber List (moderate evidence)
Skeletal dysplasia v2.121 COPB2 Eleanor Williams Added comment: Comment on list classification: Gene copied from the Osteogenesis imperfecta panel. Leaving as amber for now, but there are 2 cases with fractures and 4 with osteopaenia, plus a mouse model with low bone mass, so sufficient to rate green after then next GMS review.
Skeletal dysplasia v2.121 COPB2 Eleanor Williams Gene: copb2 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.120 COPB2 Eleanor Williams Entity copied from Osteogenesis imperfecta v2.36
Skeletal dysplasia v2.120 COPB2 Eleanor Williams gene: COPB2 was added
gene: COPB2 was added to Skeletal dysplasia. Sources: NHS GMS,Expert list,Expert Review Amber
Q3_21_rating, watchlist_moi tags were added to gene: COPB2.
Mode of inheritance for gene: COPB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COPB2 were set to 34450031; 29036432
Phenotypes for gene: COPB2 were set to juvenile osteoporosis; Osteopenia; Osteoporosis; recurrent fractures
Skeletal dysplasia v2.119 LRRK1 Conor Pallatt gene: LRRK1 was added
gene: LRRK1 was added to Skeletal dysplasia. Sources: NHS GMS,Literature
Mode of inheritance for gene: LRRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRK1 were set to 27829680; 27055475; 31571209; 32119750
Phenotypes for gene: LRRK1 were set to Osteosclerotic metaphyseal dysplasia (OSMD) (OMIM: 615198)
Penetrance for gene: LRRK1 were set to Complete
Review for gene: LRRK1 was set to GREEN
Added comment: A detailed phenotypic picture of Osteosclerotic metaphyseal dysplasia (OSMD) in patients with LRRK1 variants can be seen in table 1 of Howaldt et al (2020).

Lida et al (2016) identified homozygous deletion that is predicted to result in elongation of protein (p.E1980Afs*66) in a child with OSMD. Child was born to consanguineous parents, both heterozygous for variant.

Guo et al (2017) identified a family with OSMD. Healthy, non-consanguineous parents have two children with OSMD that are homozygous for 1bp insertion in LRRK1 that is predicted to result in a frame-shift and produce an elongated protein (p.A1991Gfs*31) without nonsense-mediated mRNA decay. A similar effect seen in Lida et al (2016).

Howaldt et al (2020) shows a patient with a homozygous splice site mutation resulting in near complete skipping of exon 3 in cDNA leading to a frameshift (p.Ala34Profs*33). The variant segregated with disorder in the family with parents being heterozygous for the variant and clinically unaffected.

Miryounesi et al (2020) identified a patient with suspected OSMD from healthy, consanguineous parents. Patient is homozygous for stop gain mutation (c.2785G > T, p.E929X) in LRRK1. Parents are heterozygous for the variant.

Homozygous nonsense variant in LRRK1 also identified in an individual recruited to the 100,000 genomes project for skeletal dysplasia, Osteosclerotic metaphyseal dysplasia is considered a good fit for phenotype.

LRRK1 gene should be included in the skeletal dysplasia panel as a green gene at the next GMS panel update.
Sources: NHS GMS, Literature
Skeletal dysplasia v2.119 MYO1H Sarah Leigh Entity copied from Familial dysautonomia v1.15
Skeletal dysplasia v2.119 MYO1H Sarah Leigh gene: MYO1H was added
gene: MYO1H was added to Skeletal dysplasia. Sources: Expert Review Red,Literature
Mode of inheritance for gene: MYO1H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYO1H were set to 28779001
Phenotypes for gene: MYO1H were set to ?Central hypoventilation syndrome, congenital, 2, and autonomic dysfunction OMIM:619482
Skeletal dysplasia v2.118 SPARC Arina Puzriakova Phenotypes for gene: SPARC were changed from Osteogenesis imperfecta, type XVII 616507 to Osteogenesis imperfecta, type XVII, OMIM:616507
Skeletal dysplasia v2.117 SPARC Arina Puzriakova Publications for gene: SPARC were set to 26027498
Skeletal dysplasia v2.116 GJA1 Arina Puzriakova Phenotypes for gene: GJA1 were changed from Oculodentodigital dysplasia 164200; Syndactyly, type III 186100; Erythrokeratodermia variabilis et progressiva 133200; Palmoplantar keratoderma with congenital alopecia 104100; Oculodentodigital dysplasia, autosomal recessive 257850; Craniometaphyseal dysplasia, autosomal recessive 218400; Hypoplastic left heart syndrome 1 241550 to Craniometaphyseal dysplasia, autosomal recessive, OMIM:218400; Oculodentodigital dysplasia, OMIM:164200; Oculodentodigital dysplasia, autosomal recessive, OMIM:257850; Syndactyly, type III, OMIM:186100
Skeletal dysplasia v2.115 DLX5 Arina Puzriakova Tag Q3_21_NHS_review tag was added to gene: DLX5.
Skeletal dysplasia v2.115 FIG4 Sarah Leigh Added comment: Comment on phenotypes: Amyotrophic lateral sclerosis 11 OMIM:612577 is not relevant to this panel
Skeletal dysplasia v2.115 FIG4 Sarah Leigh Phenotypes for gene: FIG4 were changed from Yunis-Varon syndrome 216340; Amyotrophic lateral sclerosis 11 612577; Yunis-Varon syndrome 216340 to Charcot-Marie-Tooth disease, type 4J, OMIM:611228; Charcot-Marie-Tooth disease type 4J MONDO:0012640; Yunis Varon syndrome OMIM:216340; Yunis-Varon syndrome MONDO:0008995
Skeletal dysplasia v2.114 DLX5 Ivone Leong Phenotypes for gene: DLX5 were changed from Split-hand/foot malformation 1 with sensorineural hearing loss 220600 to ?Split-hand/foot malformation 1 with sensorineural hearing loss, OMIM:220600; Split-hand/foot malformation 1, OMIM:183600
Skeletal dysplasia v2.113 DLX5 Ivone Leong Tag Q3_21_MOI tag was added to gene: DLX5.
Skeletal dysplasia v2.113 DLX5 Ivone Leong reviewed gene: DLX5: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.113 TBX4 Ivone Leong Phenotypes for gene: TBX4 were changed from Ischiocoxopodopatellar syndrome 147891; Ischiocoxopodopatellar syndrome 147891 to Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension, OMIM:147891
Skeletal dysplasia v2.112 WNT1 Ivone Leong Phenotypes for gene: WNT1 were changed from {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, OMIM:615221; Osteogenesis imperfecta, type XV, 615220 to {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, OMIM:615221; Osteogenesis imperfecta, type XV, OMIM:615220
Skeletal dysplasia v2.111 WNT1 Ivone Leong Phenotypes for gene: WNT1 were changed from osteogenesis imperfecta; OI/osteoporosis; {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, 615221; Osteogenesis imperfecta, type XV, 615220 to {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, OMIM:615221; Osteogenesis imperfecta, type XV, 615220
Skeletal dysplasia v2.110 LTBP1 Eleanor Williams changed review comment from: Short stature was noted in 8/8 (100%) of the patients reported in PMID:33991472; to: Short stature was noted in 8/8 (100%) and Genua vara (bow-leggedness) in 3/8 (37.5) of the patients reported in PMID:33991472
Skeletal dysplasia v2.110 LTBP1 Eleanor Williams commented on gene: LTBP1: Short stature was noted in 8/8 (100%) of the patients reported in PMID:33991472
Skeletal dysplasia v2.110 LTBP1 Eleanor Williams Added comment: Comment on phenotypes: OMIM phenotype added 28-07-2021
Skeletal dysplasia v2.110 LTBP1 Eleanor Williams Phenotypes for gene: LTBP1 were changed from inherited cutis laxa MONDO:0100237 to inherited cutis laxa MONDO:0100237; Cutis laxa, autosomal recessive, type IIE, OMIM:619451
Skeletal dysplasia v2.109 SMAD3 Eleanor Williams commented on gene: SMAD3: Note one case with a biallelic variant reported:
PMID: 32935439 - Baskin et al 2020 - first report of a LDS patient with biallelic SMAD3 variants (affecting splice site). Proband had classic Loeys-Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected.
Skeletal dysplasia v2.109 BMPR1B Arina Puzriakova Phenotypes for gene: BMPR1B were changed from Brachydactyly, type A1, D 616849; Brachydactyly, type A2 112600; Acromesomelic dysplasia, Demirhan type 609441 to Acromesomelic dysplasia, Demirhan type, OMIM:609441; Brachydactyly, type A1, D, OMIM:616849; Brachydactyly, type A2, OMIM:112600
Skeletal dysplasia v2.108 WNT10B Ivone Leong Phenotypes for gene: WNT10B were changed from Split-hand/foot malformation 6 225300 to Split-hand/foot malformation 6, OMIM:225300
Skeletal dysplasia v2.107 FLNA Arina Puzriakova Phenotypes for gene: FLNA were changed from Terminal osseous dysplasia 300244; Otopalatodigital syndrome, type II -304120; Otopalatodigital syndrome, type II 304120 XLD; Otopalatodigital syndrome, type I -311300; Melnick Needles syndrome 309350; Frontometaphyseal dysplasia 305620; Frontometaphyseal dysplasia 305620 XLR; Osteodysplasty Melnick Needles 309350 XLD to Frontometaphyseal dysplasia 1, OMIM:305620; Melnick-Needles syndrome, OMIM:309350; Otopalatodigital syndrome, type I, OMIM:311300; Otopalatodigital syndrome, type II, OMIM:304120; Terminal osseous dysplasia, OMIM:300244
Skeletal dysplasia v2.106 DLX5 Tracy Lester edited their review of gene: DLX5: Added comment: This gene is primarily monoallelic inheritance, many families reported. Biallelic inheritance has been rarely reported and seems to result in a more severe phenotype with deafness as well. Please update mode of inheritance to include monoallelic as well as biallelic, as a variant in this gene was almost missed because it was not in the tier 1 and 2. Thanks; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Set current diagnostic: yes
Skeletal dysplasia v2.106 WBP11 Ivone Leong Phenotypes for gene: WBP11 were changed from malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems to Vertebral, cardiac, tracheoesophageal, renal, and limb defects, OMIM:619227
Skeletal dysplasia v2.105 SLCO2A1 Zornitza Stark reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23509104, 27134495, 33852188, 22331663, 27134495; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.105 DPM1 Arina Puzriakova Phenotypes for gene: DPM1 were changed from Congenital disorder of glycosylation, type Ie 608799 to Congenital disorder of glycosylation, type Ie, OMIM:608799
Skeletal dysplasia v2.104 RPL13 Arina Puzriakova Added comment: Comment on phenotypes: RPL13 is now associated with a relevant phenotype in OMIM - Spondyloepimetaphyseal dysplasia, Isidor-Toutain type, MIM# 618728
Skeletal dysplasia v2.104 RPL13 Arina Puzriakova Phenotypes for gene: RPL13 were changed from Spondyloepimetaphyseal Dysplasia with Severe Short Stature to Spondyloepimetaphyseal dysplasia, Isidor-Toutain type, OMIM:618728
Skeletal dysplasia v2.103 FZD2 Arina Puzriakova Phenotypes for gene: FZD2 were changed from Autosomal dominant omodysplasia type 2 164745; Autosomal dominant omodysplasia 164745 to Omodysplasia 2, OMIM:164745; Robinow syndrome
Skeletal dysplasia v2.102 SLC17A5 Arina Puzriakova Phenotypes for gene: SLC17A5 were changed from Sialic acid storage disorder, infantile 269920 to Salla disease, OMIM:604369; Sialic acid storage disorder, infantile, OMIM:269920
Skeletal dysplasia v2.101 ARCN1 Andžela Lazdāne edited their review of gene: ARCN1: Changed rating: GREEN
Skeletal dysplasia v2.101 FAM46A Arina Puzriakova Phenotypes for gene: FAM46A were changed from Osteogenesis imperfecta, type XVIII 617952 to Osteogenesis imperfecta, type XVIII, OMIM:617952
Skeletal dysplasia v2.100 ARCN1 Andžela Lazdāne gene: ARCN1 was added
gene: ARCN1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: ARCN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARCN1 were set to PMID: 27476655
Phenotypes for gene: ARCN1 were set to Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay
Penetrance for gene: ARCN1 were set to Complete
Review for gene: ARCN1 was set to AMBER
Added comment: Clinical features like short stature, rhizomelia, laxity of the small joints, cleft palete and developmental delay also tend to occur in Skeletal dysplasia.

ARCN1 gene encodes the coatomer subunit delta of COPI which is a coatomer protein complex responsible for intracellular protein transport. The importance of this mechanisms is underscored by various skeletal disorders. COPI-mediated transport is important in human development, including skeletogenesis and brain growth.
Sources: Literature
Skeletal dysplasia v2.100 MYO18B Andžela Lazdāne gene: MYO18B was added
gene: MYO18B was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: MYO18B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYO18B were set to PMID: 32637634
Phenotypes for gene: MYO18B were set to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism
Penetrance for gene: MYO18B were set to Complete
Review for gene: MYO18B was set to AMBER
Added comment: Truncating mutations of MYO18B have been found to cause nemaline myopathy with cardiomyopathy or Klippel-Feil syndrome (KFS). Other KFS genes such as GDF3, GDF6, MEOX1, and RIPPLY2 are include in Skeletal dysplasia panel. KFS patients may have symptoms like spinal instability, disc degeneration, scoliosis, short neck, cleft palate, facial dysmorphism, and limb and hand abnormalities which may also be present in Skeletal dysplasia.
Sources: Literature
Skeletal dysplasia v2.100 GLI3 Arina Puzriakova Publications for gene: GLI3 were set to
Skeletal dysplasia v2.99 GLI3 Arina Puzriakova reviewed gene: GLI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32591344; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.99 LTBP1 Sarah Leigh Classified gene: LTBP1 as Amber List (moderate evidence)
Skeletal dysplasia v2.99 LTBP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Skeletal dysplasia v2.99 LTBP1 Sarah Leigh Gene: ltbp1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.98 LTBP1 Sarah Leigh gene: LTBP1 was added
gene: LTBP1 was added to Skeletal dysplasia. Sources: Literature
Q2_21_rating tags were added to gene: LTBP1.
Mode of inheritance for gene: LTBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTBP1 were set to 33991472
Phenotypes for gene: LTBP1 were set to inherited cutis laxa MONDO:0100237
Review for gene: LTBP1 was set to GREEN
Added comment: Not associated with relevant phenotype in OMIM or Gen2Phen (as of 18/05/20210). At least four terminating variants were reported in unrelated cases. Supportive in vitro and in vivo studies demonstrate the role of LTBP1 in skin and bone ECM assembly and homeostasis, in human and zebrafish (PMID 33991472).
Sources: Literature
Skeletal dysplasia v2.97 NEPRO Zornitza Stark gene: NEPRO was added
gene: NEPRO was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: NEPRO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
Phenotypes for gene: NEPRO were set to Anauxetic dysplasia 3, MIM618853
Review for gene: NEPRO was set to AMBER
Added comment: PMIDs 26633546, 29620724: 2 families with the same homozygous missense variant, haplotype analysis confirmed the founder nature of the variant. PMID 31250547: 1 family with homozygous novel missense All 5 affected individuals have severe short stature, brachydactyly, skin laxity, joint hypermobility, and joint dislocations. They also have short metacarpals, broad middle phalanges, and metaphyseal irregularities. No functional studies.
Sources: Literature
Skeletal dysplasia v2.97 UFSP2 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases with skeletal dysplasia (OMIM:142669 & OMIM:617974). Supportive functional studies presented for one of the variants (PMID 26428751).; to: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases with skeletal dysplasia (OMIM:142669 & OMIM:617974), within the UFSP2 C-terminal C78 peptidase domain, which is required for its catalytic activity. Supportive functional studies presented for one of the variants (PMID 26428751) .
Skeletal dysplasia v2.97 UFSP2 Sarah Leigh Publications for gene: UFSP2 were set to 28892125; 26428751; 32755715
Skeletal dysplasia v2.96 UFSP2 Sarah Leigh Added comment: Comment on phenotypes: A biallelic variant rs142500730 has been associated with pediatric neurodevelopmental anomalies and epilepsy (PMID 33473208).
Skeletal dysplasia v2.96 UFSP2 Sarah Leigh Phenotypes for gene: UFSP2 were changed from ?Beukes Hip Dysplasia OMIM:142669; hip dysplasia, Beukes type MONDO:0007726; ?Spondyloepimetaphyseal dysplasia, Di Rocco type OMIM:617974; spondyloepimetaphyseal dysplasia, di rocco type MONDO:0060702 to ?Beukes Hip Dysplasia OMIM:142669; hip dysplasia, Beukes type MONDO:0007726; ?Spondyloepimetaphyseal dysplasia, Di Rocco type OMIM:617974; spondyloepimetaphyseal dysplasia, di rocco type MONDO:0060702
Skeletal dysplasia v2.95 UFSP2 Sarah Leigh Classified gene: UFSP2 as Amber List (moderate evidence)
Skeletal dysplasia v2.95 UFSP2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Skeletal dysplasia v2.95 UFSP2 Sarah Leigh Gene: ufsp2 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.94 UFSP2 Sarah Leigh Tag Q2_21_rating tag was added to gene: UFSP2.
Skeletal dysplasia v2.94 UFSP2 Sarah Leigh reviewed gene: UFSP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v2.94 UFSP2 Sarah Leigh Mode of inheritance for gene: UFSP2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.93 UFSP2 Sarah Leigh Phenotypes for gene: UFSP2 were changed from Beukes Hip Dysplasia 142669, Spondyloepimetaphyseal dysplasia, Di Rocco type 617974 to ?Beukes Hip Dysplasia OMIM:142669; hip dysplasia, Beukes type MONDO:0007726; ?Spondyloepimetaphyseal dysplasia, Di Rocco type OMIM:617974; spondyloepimetaphyseal dysplasia, di rocco type MONDO:0060702
Skeletal dysplasia v2.92 UFSP2 Sarah Leigh Publications for gene: UFSP2 were set to 28892125; 26428751
Skeletal dysplasia v2.91 FBN2 Sarah Leigh Deleted their comment
Skeletal dysplasia v2.91 FBN2 Sarah Leigh commented on gene: FBN2: It would appear from PMIDs 33571691, 25558065 & 28383543 that biallelic variants should be considered for this gene and as such the MOI should be changed to BOTH monallelic and biallelic, autosomal or pseudoautosomal.
Skeletal dysplasia v2.91 FBN2 Sarah Leigh edited their review of gene: FBN2: Added comment: It would appear from PMIDs 33571691, 25558065 & 28383543 that biallelic variants should be considered for this gene and as such the MOI should be changed to BOTH monallelic and biallelic, autosomal or pseudoautosomal.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.91 FBN2 Sarah Leigh Phenotypes for gene: FBN2 were changed from Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363 to Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363
Skeletal dysplasia v2.90 FBN2 Sarah Leigh Phenotypes for gene: FBN2 were changed from Contractural arachnodactyly, congenital 121050 to Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363
Skeletal dysplasia v2.89 FBN2 Sarah Leigh Publications for gene: FBN2 were set to 7493032; 33571691; 25558065; 28383543
Skeletal dysplasia v2.88 FBN2 Sarah Leigh Publications for gene: FBN2 were set to
Skeletal dysplasia v2.87 FBN2 Sarah Leigh Tag Q2_21_MOI tag was added to gene: FBN2.
Skeletal dysplasia v2.87 NMNAT1 Zornitza Stark gene: NMNAT1 was added
gene: NMNAT1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: NMNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT1 were set to 32533184
Phenotypes for gene: NMNAT1 were set to Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), MIM#619260
Review for gene: NMNAT1 was set to GREEN
gene: NMNAT1 was marked as current diagnostic
Added comment: The association with LCA is well established.

New report of a syndromic LCA disorder and note also unusual variant type. Three families, but two are distantly related (shared haplotype). The affected children in those two families were homozygous for 7.4-kb duplication involving the last 2 exons of the NMNAT1 gene, spanning the beginning of intron 3 to the middle of the 3-prime UTR (chr1:10,036,359-10,043,727, GRCh37). The third affected individual was compound het for the duplication and a splicing variant.
Sources: Literature
Skeletal dysplasia v2.87 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Polydactyly; Bardet-Biedl syndrome 1 209900 to Polydactyly; Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Skeletal dysplasia v2.86 SCUBE3 Sarah Leigh Phenotypes for gene: SCUBE3 were changed from to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies OMIM:619184
Skeletal dysplasia v2.85 SCUBE3 Sarah Leigh edited their review of gene: SCUBE3: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 5 variants reported in 5 unrelated cases, together with supportive functional and mouse model studies (PMID 33308444).; Changed rating: GREEN
Skeletal dysplasia v2.85 SCUBE3 Sarah Leigh Classified gene: SCUBE3 as Amber List (moderate evidence)
Skeletal dysplasia v2.85 SCUBE3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Skeletal dysplasia v2.85 SCUBE3 Sarah Leigh Gene: scube3 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.84 SCUBE3 Sarah Leigh Tag Q2_21_rating tag was added to gene: SCUBE3.
Skeletal dysplasia v2.84 SCUBE3 Sarah Leigh Publications for gene: SCUBE3 were set to
Skeletal dysplasia v2.83 EN1 Zornitza Stark gene: EN1 was added
gene: EN1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: EN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EN1 were set to 33568816
Phenotypes for gene: EN1 were set to ENDOVE syndrome, limb-only type, MIM# 619217; ENDOVE syndrome, limb-brain type, MIM# 619218
Review for gene: EN1 was set to GREEN
gene: EN1 was marked as current diagnostic
Added comment: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some.

Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene.

Mouse model recapitulated the phenotype.

An additional fourth individual had cerebellar hypoplasia in addition to the skeletal phenotype, and a bi-allelic LoF variant.
Sources: Literature
Skeletal dysplasia v2.83 ATXN10_ATTCT Arina Puzriakova Tag curated_removed tag was added to STR: ATXN10_ATTCT.
Skeletal dysplasia v2.83 ZIC1 Arina Puzriakova Tag curated_removed tag was added to gene: ZIC1.
Skeletal dysplasia v2.83 TWIST2 Arina Puzriakova Tag curated_removed tag was added to gene: TWIST2.
Skeletal dysplasia v2.83 TGFBR1 Arina Puzriakova Tag curated_removed tag was added to gene: TGFBR1.
Skeletal dysplasia v2.83 TCF12 Arina Puzriakova Tag curated_removed tag was added to gene: TCF12.
Skeletal dysplasia v2.83 KAT6A Arina Puzriakova Tag curated_removed tag was added to gene: KAT6A.
Skeletal dysplasia v2.83 IGF1R Arina Puzriakova Tag curated_removed tag was added to gene: IGF1R.
Skeletal dysplasia v2.83 EFNB1 Arina Puzriakova Tag curated_removed tag was added to gene: EFNB1.
Skeletal dysplasia v2.83 TCTEX1D2 Catherine Snow Tag new-gene-name tag was added to gene: TCTEX1D2.
Skeletal dysplasia v2.83 TCTEX1D2 Catherine Snow commented on gene: TCTEX1D2
Skeletal dysplasia v2.83 WBP11 Eleanor Williams Tag Q2_21_rating tag was added to gene: WBP11.
Skeletal dysplasia v2.83 WBP11 Eleanor Williams Classified gene: WBP11 as Amber List (moderate evidence)
Skeletal dysplasia v2.83 WBP11 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber with recommendation for a green rating following GMS review.
Skeletal dysplasia v2.83 WBP11 Eleanor Williams Gene: wbp11 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.82 WBP11 Eleanor Williams gene: WBP11 was added
gene: WBP11 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WBP11 were set to 33276377
Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems
Review for gene: WBP11 was set to GREEN
Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.

Vertebral anomalies were noted in 6/13 patients from 5 families. One patient had congenital scoliosis and one abnormalities of the right upper ribs. Genomics England clinical team suggest it just meets the threshold for the skeletal dysplasia panel.
Sources: Literature
Skeletal dysplasia v2.81 TBXAS1 Ivone Leong Tag for-review tag was added to gene: TBXAS1.
Skeletal dysplasia v2.81 GZF1 Ivone Leong Tag for-review tag was added to gene: GZF1.
Skeletal dysplasia v2.81 PKDCC Ivone Leong commented on gene: PKDCC
Skeletal dysplasia v2.81 PKDCC Ivone Leong Tag for-review tag was added to gene: PKDCC.
Skeletal dysplasia v2.81 SMAD6 Ivone Leong Classified gene: SMAD6 as Amber List (moderate evidence)
Skeletal dysplasia v2.81 SMAD6 Ivone Leong Added comment: Comment on list classification: New gene added by Tracy Lester (Genetics laboratory, Oxford UK). This gene is associated with a phenotype in OMIM and Gene2Phenotype.

Based on the available evidence it is recommended that this gene be given Green status at the next review.
Skeletal dysplasia v2.81 SMAD6 Ivone Leong Gene: smad6 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.80 SMAD6 Ivone Leong Tag for-review tag was added to gene: SMAD6.
Skeletal dysplasia v2.80 FGF9 Zornitza Stark edited their review of gene: FGF9: Set current diagnostic: yes
Skeletal dysplasia v2.80 FGF9 Zornitza Stark reviewed gene: FGF9: Rating: GREEN; Mode of pathogenicity: None; Publications: 33140402, 28730625, 19589401, 33174625; Phenotypes: Multiple synostoses syndrome 3, OMIM # 612961; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.80 TONSL Michael Oldridge reviewed gene: TONSL: Rating: GREEN; Mode of pathogenicity: None; Publications: 30773277, 30773278; Phenotypes: SPONASTRIME dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 SMAD6 Tracy Lester gene: SMAD6 was added
gene: SMAD6 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD6 were set to 31138930
Phenotypes for gene: SMAD6 were set to Radioulnar synostosis
Penetrance for gene: SMAD6 were set to Incomplete
Review for gene: SMAD6 was set to GREEN
Added comment: SMAD6 is frequently mutated in non-syndromic radioulnar synostosis.Using exome seq the authors found 16 LOF and 6 rare missense variants in sporadic cases, which was a highly significant association. The findings were replicated in a different cohort. Four cases had de novo variants and others were inherited in a dominant fashion.
SMAD6 LOF variants have also been shown to be enriched in mid-line craniosynostosis and in certain cardiac disorders. It isn't yet clear if a variant can cause different phenotypes in the same family or combinations of these phenotypes in the same individual. Genotype-phenotype correlation is not understood.
This gene is currently tested diagnostically in cases of mid-line craniosynostosis and is green on panel R100.
Sources: NHS GMS
Skeletal dysplasia v2.80 POLR1B Michael Oldridge reviewed gene: POLR1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31649276; Phenotypes: TCS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.80 PKDCC Michael Oldridge reviewed gene: PKDCC: Rating: GREEN; Mode of pathogenicity: None; Publications: 30478137; Phenotypes: rhizomelic limb shortening, facial dysmorphism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 NXN Michael Oldridge changed review comment from: 2 unrelated families with recessive Robinow syndrome (RRS), one hom and one comp het for variants, segregation fits with recessive inheritance. Mouse model has overlapping clinical features to RRS . Gene expressed in limb bud of mice and acts in the Wnt/PCP pathway, as do the DVL genes, WNT5A and ROR2, genes also associated with the very specific RRS phenotype.; to: 2 unrelated families with recessive Robinow syndrome (RRS), one hom and one comp het for variants, segregation fits with recessive inheritance. Mouse model has overlapping clinical features to RRS . Gene expressed in limb bud of mice and acts in the Wnt/PCP pathway, as do the DVL genes, WNT5A, FZD2 and ROR2, genes also associated with the very specific RRS phenotype.
Skeletal dysplasia v2.80 NXN Michael Oldridge changed review comment from: 2 unrelated families with recessive Robinow syndrome (RRS), one hom and one comp het for variants, segregation fits with recessive inheritance. Mouse model has overlapping clinical features to RRS . Gene expressed in limb bud of mice and acts in the Wnt/PCP pathway, as do the DVL genes and ROR2, genes also associated with the very specific RRS phenotype.; to: 2 unrelated families with recessive Robinow syndrome (RRS), one hom and one comp het for variants, segregation fits with recessive inheritance. Mouse model has overlapping clinical features to RRS . Gene expressed in limb bud of mice and acts in the Wnt/PCP pathway, as do the DVL genes, WNT5A and ROR2, genes also associated with the very specific RRS phenotype.
Skeletal dysplasia v2.80 NXN Michael Oldridge reviewed gene: NXN: Rating: GREEN; Mode of pathogenicity: None; Publications: 29276006; Phenotypes: recessive Robinow syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 KIAA1217 Michael Oldridge reviewed gene: KIAA1217: Rating: RED; Mode of pathogenicity: None; Publications: 32369272; Phenotypes: vertebral malformations; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.80 HS2ST1 Michael Oldridge reviewed gene: HS2ST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33159882; Phenotypes: ID, facial dysmorphism, skeletal abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 GNPNAT1 Michael Oldridge reviewed gene: GNPNAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32591345; Phenotypes: rhizomelic short stature; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 CSGALNACT1 Michael Oldridge reviewed gene: CSGALNACT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31705726, 27599773, 31325655; Phenotypes: Skeletal dysplasia, mild, with joint laxity and advanced bone age , MIM618870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 COG4 Michael Oldridge reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 30290151; Phenotypes: Saul-Wilson syndrome, OMIM:618150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.80 C16orf62 Michael Oldridge reviewed gene: C16orf62: Rating: AMBER; Mode of pathogenicity: None; Publications: 31712251; Phenotypes: 3C/Ritscher-Schinzel-like syndrome, MIM619135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 ANAPC1 Michael Oldridge reviewed gene: ANAPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31303264; Phenotypes: Rothmund Thomson syndrome type 1, OMIM:618625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 IFT52 Arina Puzriakova Phenotypes for gene: IFT52 were changed from SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY, SRTD16 #617102 to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Skeletal dysplasia v2.79 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia 612651 to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Skeletal dysplasia v2.78 TMEM38B Arina Puzriakova Phenotypes for gene: TMEM38B were changed from Osteogenesis imperfecta, type XIV 615066; Osteogenesis imperfecta, type XIV 615066; osteogenesis imperfecta; Osteogenesis imperfecta, type XIV, 615066 to Osteogenesis imperfecta, type XIV, OMIM:615066; Osteogenesis imperfecta type 14, MONDO:0014029
Skeletal dysplasia v2.77 TCTEX1D2 Arina Puzriakova Phenotypes for gene: TCTEX1D2 were changed from Short-rib thoracic dysplasia 17 with or without polydactyly, 617405; Short-rib thoracic dysplasia 17 with or without polydactyly, 617405 to Short-rib thoracic dysplasia 17 with or without polydactyly, OMIM:617405; Short-rib thoracic dysplasia 17 with or without polydactyly, MONDO:0054565
Skeletal dysplasia v2.76 RINT1 Eleanor Williams changed review comment from: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.; to: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM. Probable association with Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities in Gene2Phenotype.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.
Skeletal dysplasia v2.76 RINT1 Eleanor Williams changed review comment from: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF_ and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.; to: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.
Skeletal dysplasia v2.76 TBXAS1 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the mode of inheritance as BOTH for now, but with recommendation to change to just BIALLELIC following expert review that monallelic inheritance is not seen in the skeletal phenotype.
Skeletal dysplasia v2.76 TBXAS1 Eleanor Williams Mode of inheritance for gene: TBXAS1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.75 NPR3 Eleanor Williams Classified gene: NPR3 as Amber List (moderate evidence)
Skeletal dysplasia v2.75 NPR3 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber with a recommendation for green rating following GMS review. 3 unrelated cases with a similar phenotype and supporting functional data and mouse model.
Skeletal dysplasia v2.75 NPR3 Eleanor Williams Gene: npr3 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.74 NPR3 Eleanor Williams Publications for gene: NPR3 were set to PMID: 30032985; 10468599
Skeletal dysplasia v2.73 NPR3 Eleanor Williams Tag for-review tag was added to gene: NPR3.
Skeletal dysplasia v2.73 NPR3 Eleanor Williams reviewed gene: NPR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30032985, 10468599; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.73 PFN1 Eleanor Williams changed review comment from: Comment on list classification: Promoting from grey to amber. There are 3 familial cases reported but they all come from the same region of Italy and have the same variant, so possible founder effect. There is some functional data and some CNV data in addition.; to: Comment on list classification: Promoting from grey to amber. There are 3 familial cases reported but they all come from the same region of Italy and have the same variant, so possible founder effect. There is some functional data and some CNV data in addition. Wait for confirmation of this gene's involvement in Paget disease of bone in probands with different variants or that are confirmed as unrelated to the cases already described.
Skeletal dysplasia v2.73 PFN1 Eleanor Williams Phenotypes for gene: PFN1 were changed from Paget’s disease of bone to Paget’s disease of bone; bone Paget disease MONDO:0005382
Skeletal dysplasia v2.72 PFN1 Eleanor Williams Classified gene: PFN1 as Amber List (moderate evidence)
Skeletal dysplasia v2.72 PFN1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. There are 3 familial cases reported but they all come from the same region of Italy and have the same variant, so possible founder effect. There is some functional data and some CNV data in addition.
Skeletal dysplasia v2.72 PFN1 Eleanor Williams Gene: pfn1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.71 PFN1 Eleanor Williams edited their review of gene: PFN1: Changed rating: AMBER; Changed phenotypes: bone Paget disease MONDO:0005382; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.71 PFN1 Eleanor Williams commented on gene: PFN1
Skeletal dysplasia v2.71 NPR2 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the MOI as both, because there are both AD and AR inheritances associated with different types of skeletal dysplasia in OMIM.
Skeletal dysplasia v2.71 NPR2 Eleanor Williams Mode of inheritance for gene: NPR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.70 NPR2 Eleanor Williams commented on gene: NPR2: PMID: 33288834 - Simsek-Kiper et al 2020 - they investigated 26 AMDM patients from 22 unrelated families. Sanger sequencing of NPR2 was performed in 23 patients and exome sequencing was performed in 5 patients They found
NPR2 variants in 23 patients (19 were homozygotes, 4 were compound heterozygotes). 22 distinct NPR2 (NM_003995) variants (14 missense, 5 nonsense, 2 intronic, and 1 single-amino acid deletion) were detected. In 14 families, segregation analysis was performed and showed the heterozygous NPR2 carrier status of the parents. Detailed radiographic evaluations were done, showing osteopenia, shortness in long tubular bones, radial bowing and radial head dislocation in the majority of cases. Other phenotypic features included motor developmental delay (11/23), global developmental delay/intellectual disability (GDD/ID) (5/23), spinal canal stenosis (2/23), and atlantoaxial dislocation (1/23), renal abnormalities and oligodontia. However, the authors note that the high level of parental consanguinity (18 patients) might have contributed to these phenotypes, from other gene variants.
The height of carrier parents was also assessed and found to be significantly lower than controls.
Skeletal dysplasia v2.70 TMEM251 Zornitza Stark gene: TMEM251 was added
gene: TMEM251 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: TMEM251 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM251 were set to 33252156
Phenotypes for gene: TMEM251 were set to Dysostosis multiplex‐like skeletal dysplasia; severe short stature
Review for gene: TMEM251 was set to AMBER
Added comment: Two unrelated consanguineous families with homozygous variants (c.133C>T; p.Arg45Trp and c.215dupA; p.Tyr72Ter), with co-segregation data in one family. Preliminary in vitro functional assays conducted - Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes.
Sources: Literature
Skeletal dysplasia v2.70 GZF1 Eleanor Williams Phenotypes for gene: GZF1 were changed from Larsen syndrome to Larsen syndrome; joint laxity, short stature, and myopia OMIM:617662; joint laxity, short stature, and myopia MONDO:0060556
Skeletal dysplasia v2.69 GZF1 Eleanor Williams Publications for gene: GZF1 were set to 28475863
Skeletal dysplasia v2.68 GZF1 Eleanor Williams Classified gene: GZF1 as Amber List (moderate evidence)
Skeletal dysplasia v2.68 GZF1 Eleanor Williams Added comment: Comment on list classification: Leaving the rating as amber for now, but with a recommendation of green following GMS review.
Skeletal dysplasia v2.68 GZF1 Eleanor Williams Gene: gzf1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.67 GZF1 Eleanor Williams edited their review of gene: GZF1: Added comment: Associated with Joint laxity, short stature, and myopia #617662 (AR) in OMIM.

As reported by Zornitza Stark, PMID: 33009817 (Zeng et al 2020) reported two Chinese sisters who presented with severe myopia, scoliosis and hearing loss. Using WES they identified two compound heterozygous variants in GZF1 (c.397400del, p. Leu133fs; c.1474del, p. Met492fs). The parents were heterozygous carriers of the variants. Functional data showed decreased levels of HA‐tagged M492fs‐GZF1 protein and no HA-tagged L133fs‐GZF1 protein or the control vector. HA‐tagged M492fs‐GZF1 protein was also localized to the cytoplasm rather than the nuclei in which wild type protein was found.

This now brings the case number to 3.; Changed rating: GREEN; Changed publications: 33009817; Changed phenotypes: joint laxity, short stature, and myopia OMIM:617662, joint laxity, short stature, and myopia MONDO:0060556; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.67 MBTPS1 Eleanor Williams Tag for-review tag was added to gene: MBTPS1.
Skeletal dysplasia v2.67 MBTPS1 Eleanor Williams Phenotypes for gene: MBTPS1 were changed from Skeletal dysplasia to Skeletal dysplasia; ?Spondyloepiphyseal dysplasia, Kondo-Fu type OMIM:618392; spondyloepiphyseal dysplasia, kondo-fu type MONDO:0032721
Skeletal dysplasia v2.66 MBTPS1 Eleanor Williams Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013
Skeletal dysplasia v2.65 MBTPS1 Eleanor Williams Classified gene: MBTPS1 as Amber List (moderate evidence)
Skeletal dysplasia v2.65 MBTPS1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, but with recommendation of green rating following GMS review. 3 independent cases reported with biallelic variants in this gene and a skeletal phenotype.
Skeletal dysplasia v2.65 MBTPS1 Eleanor Williams Gene: mbtps1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.64 MBTPS1 Eleanor Williams reviewed gene: MBTPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32857899, 32420688, 30046013, 31070020; Phenotypes: ?Spondyloepiphyseal dysplasia, Kondo-Fu type OMIM:618392, spondyloepiphyseal dysplasia, kondo-fu type MONDO:0032721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.64 PLCB3 Eleanor Williams Phenotypes for gene: PLCB3 were changed from Spondylometaphyseal dysplasia with corneal dystrophy, MIM# 618961 to Spondylometaphyseal dysplasia with corneal dystrophy OMIM:618961; spondylometaphyseal dysplasia with corneal dystrophy MONDO:0030074
Skeletal dysplasia v2.63 PLCB3 Eleanor Williams Classified gene: PLCB3 as Red List (low evidence)
Skeletal dysplasia v2.63 PLCB3 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to red. 1 case reported and some functional data showing the effect on protein levels of the variant found.
Skeletal dysplasia v2.63 PLCB3 Eleanor Williams Gene: plcb3 has been classified as Red List (Low Evidence).
Skeletal dysplasia v2.62 PLCB3 Eleanor Williams reviewed gene: PLCB3: Rating: RED; Mode of pathogenicity: None; Publications: 29122926; Phenotypes: Spondylometaphyseal dysplasia with corneal dystrophy OMIM:618961, spondylometaphyseal dysplasia with corneal dystrophy MONDO:0030074; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.62 ANO5 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the mode of inheritance at BIALLELIC just now, but it should be changed to MONOALLELIC at the next GMS review.
Skeletal dysplasia v2.62 ANO5 Eleanor Williams Mode of inheritance for gene: ANO5 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.61 ANO5 Eleanor Williams Phenotypes for gene: ANO5 were changed from Gnatodiaphyseal dysplasia; Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias; skeletal dysplasias; Disproportionate Short Stature to Gnathodiaphyseal dysplasia OMIM:166260; gnathodiaphyseal dysplasia MONDO:0008151; Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias; skeletal dysplasias; Disproportionate Short Stature
Skeletal dysplasia v2.60 ANO5 Eleanor Williams Publications for gene: ANO5 were set to
Skeletal dysplasia v2.59 ANO5 Eleanor Williams Added comment: Comment on mode of pathogenicity: The missense variants seen in patients with Gnathodiaphyseal dysplasia are thought to act by gain-of-function
Skeletal dysplasia v2.59 ANO5 Eleanor Williams Mode of pathogenicity for gene: ANO5 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Skeletal dysplasia v2.58 ANO5 Eleanor Williams edited their review of gene: ANO5: Added comment: Associated with Gnathodiaphyseal dysplasia #166260 in OMIM with an autosomal dominant mode of inheritance. Two types of muscular dystrophy are listed with a autosomal recessive mode of inheritance.

ANO5 is also known as GDD1 and TMEM16E.

PMID: 15124103 - Tsutsumi et al 2004 - identified two heterozygous missense mutations (C356R and C356G) in ANO5/GDD1 in probands from a Japanese and an African American family with gnathodiaphyseal dysplasia.

PMID: 23047743 - Marconi et al 2013 - sequenced the ANO5 gene in a large Italian family with gnathodiaphyseal dysplasia. They identified a novel heterozygous missense mutation c.1538C-T, T513I. The mutation segregates with the disease in the family.

PMID: 32112655 - Di Zanni et al 2020 - used HEK293‐based functional assays to investigate the effects of a series of amino acid exchanges, related either to MD or GDD, at the level of the TMEM16E protein. They find a loss of TMEM16E activity for those associated with MD, and a gain‐of‐function phenotype for seven GDD‐causing mutations.; Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Changed publications: 15124103, 23047743, 32112655; Changed phenotypes: Gnathodiaphyseal dysplasia OMIM:166260, gnathodiaphyseal dysplasia MONDO:0008151; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.58 UBA2 Eleanor Williams edited their review of gene: UBA2: Changed phenotypes: split hand-foot malformation MONDO:0016576, aplasia cutis congenita (disease) MONDO:0007145, ectrodactyly
Skeletal dysplasia v2.58 UBA2 Eleanor Williams Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to split hand-foot malformation MONDO:0016576; aplasia cutis congenita (disease) MONDO:0007145; Ectrodactyly
Skeletal dysplasia v2.57 UBA2 Eleanor Williams Publications for gene: UBA2 were set to 31332306; 31587267
Skeletal dysplasia v2.56 UBA2 Eleanor Williams Classified gene: UBA2 as Amber List (moderate evidence)
Skeletal dysplasia v2.56 UBA2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber as there are two cases with SNVs reported.
Skeletal dysplasia v2.56 UBA2 Eleanor Williams Gene: uba2 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.55 UBA2 Eleanor Williams edited their review of gene: UBA2: Changed rating: AMBER; Changed publications: 31332306, 24243649, 29988626, 31587267; Changed phenotypes: split hand-foot malformation MONDO:0016576, aplasia cutis congenita (disease) MONDO:0007145; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.55 UBA2 Eleanor Williams commented on gene: UBA2
Skeletal dysplasia v2.55 POLR1B Eleanor Williams Tag for-review tag was added to gene: POLR1B.
Skeletal dysplasia v2.55 POLR1B Eleanor Williams Phenotypes for gene: POLR1B were changed from Treacher-Collins syndrome type 4 to Treacher-Collins syndrome 4 OMIM:618939; treacher collins syndrome 4 MONDO:0030067
Skeletal dysplasia v2.54 POLR1B Eleanor Williams Classified gene: POLR1B as Amber List (moderate evidence)
Skeletal dysplasia v2.54 POLR1B Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, with a recommendation for a green rating following GMS review. 5 families reported plus supportive zebrafish model.
Skeletal dysplasia v2.54 POLR1B Eleanor Williams Gene: polr1b has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.53 POLR1B Eleanor Williams edited their review of gene: POLR1B: Changed rating: GREEN; Changed publications: 31649276; Changed phenotypes: Treacher-Collins syndrome 4 OMIM:618939, treacher collins syndrome 4 MONDO:0030067; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.53 POLR1B Eleanor Williams commented on gene: POLR1B
Skeletal dysplasia v2.53 PKDCC Eleanor Williams Classified gene: PKDCC as Amber List (moderate evidence)
Skeletal dysplasia v2.53 PKDCC Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber. 2 cases plus mouse knockout, with a similar but not exactly the same phenotype to the cases reported.
Skeletal dysplasia v2.53 PKDCC Eleanor Williams Gene: pkdcc has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.52 PKDCC Eleanor Williams reviewed gene: PKDCC: Rating: AMBER; Mode of pathogenicity: None; Publications: 30478137, 19097194; Phenotypes: Rhizomelic limb shortening with dysmorphic features OMIM:618821, rhizomelic limb shortening with dysmorphic features MONDO:0032935; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.52 MIA3 Eleanor Williams Classified gene: MIA3 as Red List (low evidence)
Skeletal dysplasia v2.52 MIA3 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to red based on 1 family reported so far.
Skeletal dysplasia v2.52 MIA3 Eleanor Williams Gene: mia3 has been classified as Red List (Low Evidence).
Skeletal dysplasia v2.51 MIA3 Eleanor Williams Phenotypes for gene: MIA3 were changed from short stature; skeletal dysplasia; amelogenesis to short stature; skeletal dysplasia; amelogenesis; dentinogenesis imperfecta; short stature; brachydactyly; Platyspondyly; insulin-dependent diabetes mellitus; sensorineural hearing loss; mild intellectual disability
Skeletal dysplasia v2.50 MIA3 Eleanor Williams reviewed gene: MIA3: Rating: RED; Mode of pathogenicity: None; Publications: 32101163; Phenotypes: dentinogenesis imperfecta, short stature, brachydactyly, Platyspondyly, insulin-dependent diabetes mellitus, sensorineural hearing loss, mild intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.50 RINT1 Eleanor Williams Phenotypes for gene: RINT1 were changed from liver failure; short stature; skeletal abnormalities to liver failure; short stature; skeletal abnormalities; Infantile liver failure syndrome 3 OMIM:618641; infantile liver failure syndrome 3 MONDO:0032844
Skeletal dysplasia v2.49 RINT1 Eleanor Williams Publications for gene: RINT1 were set to PMID: 31204009
Skeletal dysplasia v2.48 RINT1 Eleanor Williams Classified gene: RINT1 as Amber List (moderate evidence)
Skeletal dysplasia v2.48 RINT1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, but with a recommendation for a green rating following GMS review. 3 cases with compound het variants in this gene.
Skeletal dysplasia v2.48 RINT1 Eleanor Williams Gene: rint1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.47 RINT1 Eleanor Williams Tag for-review tag was added to gene: RINT1.
Skeletal dysplasia v2.47 RINT1 Eleanor Williams edited their review of gene: RINT1: Changed rating: GREEN; Changed publications: 31204009; Changed phenotypes: Infantile liver failure syndrome 3 OMIM:618641, infantile liver failure syndrome 3 MONDO:0032844; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.47 RINT1 Eleanor Williams commented on gene: RINT1
Skeletal dysplasia v2.47 B9D1 Arina Puzriakova Phenotypes for gene: B9D1 were changed from Meckel syndrome 9 614209 to Meckel syndrome 9, OMIM:614209; Meckel syndrome 9, MONDO:0013630; Joubert syndrome 27, OMIM:617120; Joubert syndrome 27, MONDO:0014927
Skeletal dysplasia v2.46 B9D2 Arina Puzriakova Phenotypes for gene: B9D2 were changed from Meckel syndrome 10 614175 to Joubert syndrome 34, OMIM:614175; Meckel syndrome 10, OMIM:614175; Meckel syndrome, type 10, MONDO:0013609
Skeletal dysplasia v2.45 CSGALNACT1 Eleanor Williams Tag for-review tag was added to gene: CSGALNACT1.
Skeletal dysplasia v2.45 CSGALNACT1 Eleanor Williams Classified gene: CSGALNACT1 as Amber List (moderate evidence)
Skeletal dysplasia v2.45 CSGALNACT1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, but with recommendation for green rating following GMS review as there are now 4 cases reported of biallelic variants in this gene in patients with mild skeletal dysplasia.
Skeletal dysplasia v2.45 CSGALNACT1 Eleanor Williams Gene: csgalnact1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.44 CSGALNACT1 Eleanor Williams edited their review of gene: CSGALNACT1: Changed rating: GREEN
Skeletal dysplasia v2.44 CSGALNACT1 Eleanor Williams Phenotypes for gene: CSGALNACT1 were changed from Desbuquois dysplasia with mild joint laxity; non-proportionate short stature to Desbuquois dysplasia with mild joint laxity; non-proportionate short stature; Skeletal dysplasia, mild, with joint laxity and advanced bone age OMIM:618870; skeletal dysplasia, mild, with joint laxity and advanced bone age MONDO:0030029
Skeletal dysplasia v2.43 CSGALNACT1 Eleanor Williams Publications for gene: CSGALNACT1 were set to 27599773; 31325655
Skeletal dysplasia v2.42 CSGALNACT1 Eleanor Williams edited their review of gene: CSGALNACT1: Changed publications: 27599773, 31325655, 31705726
Skeletal dysplasia v2.42 CSGALNACT1 Eleanor Williams reviewed gene: CSGALNACT1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia, mild, with joint laxity and advanced bone age OMIM:618870, skeletal dysplasia, mild, with joint laxity and advanced bone age MONDO:0030029; Mode of inheritance: None
Skeletal dysplasia v2.42 SCUBE3 Zornitza Stark reviewed gene: SCUBE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33308444; Phenotypes: Short stature, skeletal abnormalities, craniofacial abnormalities, dental anomalies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v2.42 NPR2 Mehdi Montazer reviewed gene: NPR2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: https://doi.org/10.1038/s10038-020-00871-0; Phenotypes: Acromesomelic dysplasia, Maroteaux type (OMIM: # 602875); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.42 SMC1A Arina Puzriakova Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome 2 300590 to Cornelia de Lange syndrome 2, OMIM:300590; Cornelia de Lange syndrome 2, MONDO:0010370
Skeletal dysplasia v2.41 HSPG2 Arina Puzriakova Phenotypes for gene: HSPG2 were changed from Dyssegmental dysplasia, Silverman-Handmaker type 224410; Schwartz-Jampel syndrome, type 1 255800 to Schwartz-Jampel syndrome, type 1, OMIM:255800; Schwartz-Jampel syndrome, MONDO:0009717; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140
Skeletal dysplasia v2.40 HS2ST1 Ivone Leong Classified gene: HS2ST1 as Amber List (moderate evidence)
Skeletal dysplasia v2.40 HS2ST1 Ivone Leong Gene: hs2st1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.39 HS2ST1 Ivone Leong gene: HS2ST1 was added
gene: HS2ST1 was added to Skeletal dysplasia. Sources: Literature
for-review tags were added to gene: HS2ST1.
Mode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HS2ST1 were set to 33159882
Phenotypes for gene: HS2ST1 were set to Intellectual disability; dysmorphic features; congenital anomalies
Review for gene: HS2ST1 was set to AMBER
Added comment: This gene is not associated with a relevant phenotype in OMIM or Gene2Phenotype. Only 2 of 3 unrelated families with affected individuals described in PMID: 33159882 were reported to have ID. The affected individuals in the third family could not be assessed for ID. Other features affected individuals had were muscular hypotonia, hypoplasia/agenesis of corpus callosum, skeletal abnormalities, uni/bilateral renal agenesis (2/3) and craniofacial dysmorphism. After consulting the Genomics England Clinical Team, it was decided that this gene should be added to this panel with an Amber rating. The skeletal phenotype is relatively mild and the GMS specialist group should review whether this gene is appropriate for this panel.
Sources: Literature
Skeletal dysplasia v2.38 COG4 Ivone Leong Classified gene: COG4 as Amber List (moderate evidence)
Skeletal dysplasia v2.38 COG4 Ivone Leong Gene: cog4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.37 COG4 Ivone Leong gene: COG4 was added
gene: COG4 was added to Skeletal dysplasia. Sources: Literature
for-review tags were added to gene: COG4.
Mode of inheritance for gene: COG4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COG4 were set to 31949312; 30290151
Phenotypes for gene: COG4 were set to Saul-Wilson syndrome, OMIM:618150; microcephalic osteodysplastic dysplasia, Saul-Wilson type, MONDO:0019407
Mode of pathogenicity for gene: COG4 was set to Other
Review for gene: COG4 was set to AMBER
Added comment: This gene is associated with a phenotype in OMIM and Gene2Phenotype. This gene was added to the Cataracts panel by Zornitza Stark (Australian Genomics).

"Saul-Wilson syndrome (AD): 14 patients reported with DD, skeletal changes, cataracts, and growth retardation (progeriod like) All have a recurrent de novo heterozygous missense variant (p.Gly516Arg). Please note bi-allelic variants cause CDG. Sources: Expert list
Zornitza Stark (Australian Genomics), 7 Jul 2020"

PMID: 30290151 suggests that the Saul-Wilson syndrome variant is gain of function. Therefore, this gene should be considered to be Green at the next review.
Sources: Literature
Skeletal dysplasia v2.36 MIA3 Aleš Maver changed review comment from: The MIA3 gene is synonymous with TANGO1 in PMID:32101163. This publication reports a synonymous substitution (NM_001324062.1:c.3621A > G) that results in functionally validated exon eight skipping, leading to a truncated TANGO1/MIA3 protein. The variant was identified in four homozygous affected sibs of a consanguineous family, that presented with severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the truncated TANGO1/MIA3 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1/MIA3 impairs cellular collagen I secretion (PMID:32101163).
Sources: Literature; to: The MIA3 gene is synonymous with TANGO1 in PMID:32101163. This publication reports a synonymous substitution (NM_001324062.1:c.3621A > G) that results in functionally validated exon eight skipping, leading to a truncated TANGO1/MIA3 protein. The variant was identified in four homozygous affected sibs of a consanguineous family, that presented with severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the truncated TANGO1/MIA3 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1/MIA3 impairs cellular collagen I secretion (PMID:32101163).
Sources: Literature
Skeletal dysplasia v2.36 MIA3 Aleš Maver changed review comment from: The MIA3 gene is synonymous with TANGO1 in PMID:32101163. This publications reports a synonymous substitution (NM_001324062.1:c.3621A > G) that results in functionally validated exon eight skipping, leading to a truncated TANGO1/MIA3 protein. The variant was identified in four homozygous affected sibs of a consanguineous family, that presented with severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the truncated TANGO1/MIA3 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1/MIA3 impairs cellular collagen I secretion (PMID:32101163).
Sources: Literature; to: The MIA3 gene is synonymous with TANGO1 in PMID:32101163. This publication reports a synonymous substitution (NM_001324062.1:c.3621A > G) that results in functionally validated exon eight skipping, leading to a truncated TANGO1/MIA3 protein. The variant was identified in four homozygous affected sibs of a consanguineous family, that presented with severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the truncated TANGO1/MIA3 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1/MIA3 impairs cellular collagen I secretion (PMID:32101163).
Sources: Literature
Skeletal dysplasia v2.36 MIA3 Aleš Maver gene: MIA3 was added
gene: MIA3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIA3 were set to 32101163
Phenotypes for gene: MIA3 were set to short stature; skeletal dysplasia; amelogenesis
Penetrance for gene: MIA3 were set to unknown
Review for gene: MIA3 was set to RED
Added comment: The MIA3 gene is synonymous with TANGO1 in PMID:32101163. This publications reports a synonymous substitution (NM_001324062.1:c.3621A > G) that results in functionally validated exon eight skipping, leading to a truncated TANGO1/MIA3 protein. The variant was identified in four homozygous affected sibs of a consanguineous family, that presented with severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the truncated TANGO1/MIA3 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1/MIA3 impairs cellular collagen I secretion (PMID:32101163).
Sources: Literature
Skeletal dysplasia v2.36 ANAPC1 Ivone Leong changed review comment from: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. PMID: 31303264 describes 10 patients from 7 families with Rothmund-Thomson syndrome. 4 of 7 families are homozygous for the same intronic variant (c.2705-198C-T) and the remaining 3 affected families are compound heterozygous (c.2705-198C-T with another variant in the gene). 5/10 affected individuals have skeletal abnormalities; however, the phenotype is weak. Therefore, this gene has been given an Amber rating.
Sources: Literature; to: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. PMID: 31303264 describes 10 patients from 7 families with Rothmund-Thomson syndrome. 4 of 7 families are homozygous for the same intronic variant (c.2705-198C-T) and the remaining 3 affected families are compound heterozygous (c.2705-198C-T with another variant in the gene). 5/10 affected individuals have skeletal abnormalities; however, the phenotype is weak. Therefore, this gene has been given an Amber rating.

Have tagged with "for-review" so that GMS could review whether this gene is appropriate for the panel or not.
Sources: Literature
Skeletal dysplasia v2.36 ANAPC1 Ivone Leong Tag for-review tag was added to gene: ANAPC1.
Skeletal dysplasia v2.36 ANAPC1 Ivone Leong Classified gene: ANAPC1 as Amber List (moderate evidence)
Skeletal dysplasia v2.36 ANAPC1 Ivone Leong Gene: anapc1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.35 ANAPC1 Ivone Leong gene: ANAPC1 was added
gene: ANAPC1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: ANAPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANAPC1 were set to 31303264
Phenotypes for gene: ANAPC1 were set to Rothmund Thomson syndrome type 1, OMIM:618625, MONDO:0016368
Review for gene: ANAPC1 was set to AMBER
Added comment: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. PMID: 31303264 describes 10 patients from 7 families with Rothmund-Thomson syndrome. 4 of 7 families are homozygous for the same intronic variant (c.2705-198C-T) and the remaining 3 affected families are compound heterozygous (c.2705-198C-T with another variant in the gene). 5/10 affected individuals have skeletal abnormalities; however, the phenotype is weak. Therefore, this gene has been given an Amber rating.
Sources: Literature
Skeletal dysplasia v2.34 HHAT Zornitza Stark gene: HHAT was added
gene: HHAT was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HHAT were set to 24784881; 30912300
Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome 600092
Review for gene: HHAT was set to AMBER
Added comment: Two unrelated families reported. Clinical features include progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Variable features include infantile-onset seizures, dwarfism, generalized chondrodysplasia, and micromelia.
Sources: Literature
Skeletal dysplasia v2.34 TONSL Eleanor Williams Classified gene: TONSL as Amber List (moderate evidence)
Skeletal dysplasia v2.34 TONSL Eleanor Williams Added comment: Comment on list classification: updating from red to amber, but with a recommendation for green rating at the next GMS review.
Skeletal dysplasia v2.34 TONSL Eleanor Williams Gene: tonsl has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.33 TONSL Eleanor Williams Tag for-review tag was added to gene: TONSL.
Skeletal dysplasia v2.33 TONSL Eleanor Williams gene: TONSL was added
gene: TONSL was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: TONSL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TONSL were set to 32959051; 30773278; 30773277
Phenotypes for gene: TONSL were set to Spondyloepimetaphyseal dysplasia, sponastrime type OMIM:271510; spondyloepimetaphyseal dysplasia, sponastrime type MONDO:0010068
Review for gene: TONSL was set to GREEN
Added comment: Associated with Spondyloepimetaphyseal dysplasia, sponastrime type MIM#271510 (AR) in OMIM.

PMID: 30773277 - Burrage et al 2019 - identified, using WES or Sanger sequencing, compound heterozygous variants in TONSL in 9 individuals (8 families) with SPONASTRIME dysplasia. 4 other probands with SPONASTRIME dysplasia did not have biallelic variants in TONSL or in MMS22L, but two of them did have a single heterozygous variants in TONSL. The authors say they cannot exclude deep intronic, promotor variants or large intragenic rearrangements/deletions in these patients. An additional 4 individuals (3 families) with short stature of varied severity and spondylometaphyseal dysplasia with or without immunologic and hematologic abnormalities were also found to have compound heterozygous variants in TONSL.

PMID: 30773278 - Chang et al 2019 - Using WES they identified homozygous or compound heterozygous TONSL variants in 10 of 13 individuals (9 families) with SPONASTRIME dysplasia.

PMID: 32959051 - Micale et al 2020 - report a 9-year-old Italian girl with typical SPONASTRIME dysplasia who was found to have two novel missense variants in TONSL. Each parent was heterozygous for one of the variants. Both variants were found to be very rare in the gnomad database. Patient-derived fibroblasts show increased levels of spontaneous chromosomal breaks, reduced cell proliferation and enhanced apoptosis.
Sources: Literature
Skeletal dysplasia v2.32 MTX2 Ivone Leong Classified gene: MTX2 as Amber List (moderate evidence)
Skeletal dysplasia v2.32 MTX2 Ivone Leong Gene: mtx2 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.31 MTX2 Ivone Leong gene: MTX2 was added
gene: MTX2 was added to Skeletal dysplasia. Sources: Literature
for-review tags were added to gene: MTX2.
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Skeletal dysplasia; Mandibuloacral dysplasia; lipodystrophy; arterial calcification
Review for gene: MTX2 was set to GREEN
Added comment: The Genomics England Clinical Team suggested that this gene should be added to this panel as there are enough skeletal features for it to be here. Therefore, this gene has been given an Amber rating and will be promoted to Green at the next review.

Review from Zornitza Stark on the Lipodystrophy - childhood onset:
"Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Sources: Literature
Zornitza Stark (Australian Genomics), 5 Oct 2020"
Sources: Literature
Skeletal dysplasia v2.30 SCUBE3 Arina Puzriakova Classified gene: SCUBE3 as Red List (low evidence)
Skeletal dysplasia v2.30 SCUBE3 Arina Puzriakova Added comment: Comment on list classification: Rating Red as currently only one case reported with a potentially pathogenic variant associated with skeletal dysplasia. Additional cases required to corroborate causality.
Skeletal dysplasia v2.30 SCUBE3 Arina Puzriakova Gene: scube3 has been classified as Red List (Low Evidence).
Skeletal dysplasia v2.29 KDELR2 Eleanor Williams Tag for-review tag was added to gene: KDELR2.
Skeletal dysplasia v2.29 KDELR2 Eleanor Williams Phenotypes for gene: KDELR2 were changed from Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms; Osteogenesis imperfecta
Skeletal dysplasia v2.28 KDELR2 Eleanor Williams Publications for gene: KDELR2 were set to PMID: 33053334
Skeletal dysplasia v2.27 KDELR2 Eleanor Williams Classified gene: KDELR2 as Amber List (moderate evidence)
Skeletal dysplasia v2.27 KDELR2 Eleanor Williams Added comment: Comment on list classification: Changing the status from grey to amber, but with a recommendation for a green rating following GMS review.
Skeletal dysplasia v2.27 KDELR2 Eleanor Williams Gene: kdelr2 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.26 KDELR2 Eleanor Williams edited their review of gene: KDELR2: Changed rating: GREEN; Changed publications: 33053334; Changed phenotypes: Osteogenesis imperfecta; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.26 KDELR2 Eleanor Williams commented on gene: KDELR2
Skeletal dysplasia v2.26 PRKG2 Arina Puzriakova Classified gene: PRKG2 as Amber List (moderate evidence)
Skeletal dysplasia v2.26 PRKG2 Arina Puzriakova Added comment: Comment on list classification: Rating Amber but should be promoted to Green at the next GMS panel update (added 'for-review tag). Two unrelated cases exhibiting a consistent phenotype, supported by functional characterisation of harboured variants and concordant animal models.
Skeletal dysplasia v2.26 PRKG2 Arina Puzriakova Gene: prkg2 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.25 PRKG2 Arina Puzriakova Tag watchlist was removed from gene: PRKG2.
Tag for-review tag was added to gene: PRKG2.
Skeletal dysplasia v2.25 PRKG2 Arina Puzriakova edited their review of gene: PRKG2: Changed rating: GREEN
Skeletal dysplasia v2.25 PRKG2 Arina Puzriakova gene: PRKG2 was added
gene: PRKG2 was added to Skeletal dysplasia. Sources: Literature
watchlist tags were added to gene: PRKG2.
Mode of inheritance for gene: PRKG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKG2 were set to 33106379
Phenotypes for gene: PRKG2 were set to Acromesomelic dysplasia
Review for gene: PRKG2 was set to AMBER
Added comment: - PMID: 33106379 (2020) - Distinct homozygous variants in PRKG2 identified in two unrelated individuals, both with a skeletal dysplasia associated with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones.

Functional studies showed both variants result in NMD and disrupt the downstream MAPK signalling pathway in response to FGF2. The role of cGKII, encoded by PRKG2, in skeletal growth has been established in several animal models (references provided in paper).
Sources: Literature
Skeletal dysplasia v2.24 KDELR2 Dmitrijs Rots gene: KDELR2 was added
gene: KDELR2 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to PMID: 33053334
Phenotypes for gene: KDELR2 were set to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms
Penetrance for gene: KDELR2 were set to Complete
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies reported in PMID: 33053334
Sources: Literature
Skeletal dysplasia v2.24 NXN Arina Puzriakova Classified gene: NXN as Amber List (moderate evidence)
Skeletal dysplasia v2.24 NXN Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Skeletal dysplasia v2.24 NXN Arina Puzriakova Gene: nxn has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.23 NXN Arina Puzriakova Tag for-review tag was added to gene: NXN.
Skeletal dysplasia v2.23 XYLT1 Arina Puzriakova Phenotypes for gene: XYLT1 were changed from Desbuquois dysplasia 2 615777; Desbuquois dysplasia 2 615777 to Desbuquois dysplasia 2, 615777
Skeletal dysplasia v2.22 RINT1 Dmitrijs Rots gene: RINT1 was added
gene: RINT1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to PMID: 31204009
Phenotypes for gene: RINT1 were set to liver failure; short stature; skeletal abnormalities
Penetrance for gene: RINT1 were set to Complete
Review for gene: RINT1 was set to GREEN
gene: RINT1 was marked as current diagnostic
Added comment: Reported in 3 patients with similar phenotype in PMID: 31204009. Caused by one LoF allele and missense/in-frame hypomorphic allele.
Sources: Literature
Skeletal dysplasia v2.22 ISCA-37394-Loss Sarah Leigh Publications for Region: ISCA-37394-Loss were set to 25402011; 23188045
Skeletal dysplasia v2.21 GZF1 Zornitza Stark reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662, Larsen-like syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v2.21 FOXC1 Eleanor Williams Publications for gene: FOXC1 were set to 27193493
Skeletal dysplasia v2.20 FOXC1 Eleanor Williams reviewed gene: FOXC1: Rating: ; Mode of pathogenicity: None; Publications: 32720677; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v2.20 MBTPS1 Zornitza Stark gene: MBTPS1 was added
gene: MBTPS1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013
Phenotypes for gene: MBTPS1 were set to Skeletal dysplasia
Review for gene: MBTPS1 was set to GREEN
gene: MBTPS1 was marked as current diagnostic
Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature.
Sources: Literature
Skeletal dysplasia v2.20 PFN1 Zornitza Stark gene: PFN1 was added
gene: PFN1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PFN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PFN1 were set to 32392277; 31991009; 31346562; 32589291; 22801503
Phenotypes for gene: PFN1 were set to Paget’s disease of bone
Review for gene: PFN1 was set to AMBER
Added comment: A new phenotype association for this gene has been reported: Paget’s disease of bone (PDB).
Haploinsuffciency has been linked to PDB in 2 families with the same truncating frameshift variant (unsure if the families are related, both families are from the same region in Italy). Functional studies of this truncating variant showed abnormal protein aggregates (PMID: 32392277, 31991009). An osteoclast-specific conditional null mouse model confirmed the skeletal phenotype (PMID: 31346562). Missense variants in this gene have been previously associated with ALS (PMID: 22801503). Due to these different phenotype associations, it has been suggested that this gene can cause multisystem proteinopathy (PMID: 32589291).
Sources: Literature
Skeletal dysplasia v2.20 TNFRSF11A Sarah Leigh Added comment: Comment on mode of inheritance: It is suggested that the mode of inheritance for TNFRSF11A should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next major review.
Skeletal dysplasia v2.20 TNFRSF11A Sarah Leigh Mode of inheritance for gene: TNFRSF11A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.19 TNFRSF11A Sarah Leigh Tag for-review tag was added to gene: TNFRSF11A.
Skeletal dysplasia v2.19 PLEKHM1 Sarah Leigh changed review comment from: Comment on list classification: Published reports include three variants in two cases of biallielic osteropetrosis (PMID 17404618;28290981) and three monoallelic variants in three unrelated cases (PMID 17997709;27291868), however, in one of these cases the unaffected mother of the proband also carried the PLEKHM1 variant, possibly raising the issue of penetrance (PMID 21054159). A further variant was also identifed by RNA-seq analysis of Xanthogranulomatous epithelial tumor in a patient with osteopretosis, however, the zygosity of this variant was not reported (PMID 32415263).; to: Comment on list classification: Published reports include three variants in two cases of biallelic osteopetrosis (PMID 17404618;28290981) and three monoallelic variants in three unrelated cases (PMID 17997709;27291868), however, in one of these cases the unaffected mother of the proband also carried the PLEKHM1 variant, possibly raising the issue of penetrance (PMID 21054159). A further variant was also identified by RNA-seq analysis of Xanthogranulomatous epithelial tumour in a patient with osteopetrosis, however, the zygosity of this variant was not reported (PMID 32415263).
Skeletal dysplasia v2.19 PLEKHM1 Sarah Leigh Tag watchlist tag was added to gene: PLEKHM1.
Skeletal dysplasia v2.19 PLEKHM1 Sarah Leigh Classified gene: PLEKHM1 as Amber List (moderate evidence)
Skeletal dysplasia v2.19 PLEKHM1 Sarah Leigh Added comment: Comment on list classification: Published reports include three variants in two cases of biallielic osteropetrosis (PMID 17404618;28290981) and three monoallelic variants in three unrelated cases (PMID 17997709;27291868), however, in one of these cases the unaffected mother of the proband also carried the PLEKHM1 variant, possibly raising the issue of penetrance (PMID 21054159). A further variant was also identifed by RNA-seq analysis of Xanthogranulomatous epithelial tumor in a patient with osteopretosis, however, the zygosity of this variant was not reported (PMID 32415263).
Skeletal dysplasia v2.19 PLEKHM1 Sarah Leigh Gene: plekhm1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.18 PLEKHM1 Sarah Leigh Publications for gene: PLEKHM1 were set to 17404618; 27291868; 17997709; 21054159; 28290981
Skeletal dysplasia v2.17 PLEKHM1 Sarah Leigh Publications for gene: PLEKHM1 were set to 17404618; 27291868; 17997709; 21054159
Skeletal dysplasia v2.16 PLEKHM1 Sarah Leigh Publications for gene: PLEKHM1 were set to 17404618; 27291868; 17997709
Skeletal dysplasia v2.15 KIAA1217 Eleanor Williams changed review comment from: PMID: 32369272 - Al Dhaheri et al 2020 - 10 unrelated probands with vertebral malformations.  1 proband was compound heterozygous for variants in KIAA1217, the others were all heterozygous. 9 out of 11 variants are found in gnomad but a low allele frequency.  In 3 patients (including the compound het) the variants were inherited from an unaffected parent, in the other 7 patients parental DNA was not available.
Sources: Literature; to: PMID: 32369272 - Al Dhaheri et al 2020 - 10 unrelated probands with vertebral malformations.  1 proband was compound heterozygous for variants in KIAA1217, the others were all heterozygous. 9 out of 11 variants are found in gnomad but a low allele frequency.  In 3 patients (including the compound het) the variants were inherited from an unaffected parent, in the other 7 patients parental DNA was not available. Not associated with any phenotype in OMIM or Gene2Phenotype.
Sources: Literature
Skeletal dysplasia v2.15 KIAA1217 Eleanor Williams Classified gene: KIAA1217 as Amber List (moderate evidence)
Skeletal dysplasia v2.15 KIAA1217 Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team rating this gene amber. Although there are 10 cases reported, the mode of inheritance and level of penterance is not clear, and it would be useful to have more information prior to diagnostic use
Skeletal dysplasia v2.15 KIAA1217 Eleanor Williams Gene: kiaa1217 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.14 KIAA1217 Eleanor Williams Tag for-review tag was added to gene: KIAA1217.
Skeletal dysplasia v2.14 KIAA1217 Eleanor Williams gene: KIAA1217 was added
gene: KIAA1217 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: KIAA1217 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KIAA1217 were set to 32369272
Phenotypes for gene: KIAA1217 were set to vertebral malformations
Review for gene: KIAA1217 was set to AMBER
Added comment: PMID: 32369272 - Al Dhaheri et al 2020 - 10 unrelated probands with vertebral malformations.  1 proband was compound heterozygous for variants in KIAA1217, the others were all heterozygous. 9 out of 11 variants are found in gnomad but a low allele frequency.  In 3 patients (including the compound het) the variants were inherited from an unaffected parent, in the other 7 patients parental DNA was not available.
Sources: Literature
Skeletal dysplasia v2.13 PISD Arina Puzriakova Classified gene: PISD as Amber List (moderate evidence)
Skeletal dysplasia v2.13 PISD Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN on the next major review - at least five unrelated families (three with the same founder variant) presenting skeletal dysplasia associated with biallelic variants in this gene.
Skeletal dysplasia v2.13 PISD Arina Puzriakova Gene: pisd has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.12 PISD Arina Puzriakova gene: PISD was added
gene: PISD was added to Skeletal dysplasia. Sources: Literature
for-review tags were added to gene: PISD.
Mode of inheritance for gene: PISD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PISD were set to 31263216; 30858161; 30488656; 3561949
Phenotypes for gene: PISD were set to Liberfarb syndrome, 618889
Review for gene: PISD was set to GREEN
Added comment: Associated with Liberfarb syndrome in OMIM, but not in G2P.

PMID: 31263216 (2019) - In two sets of brothers from unrelated consanguineous families, sequencing revealed homozygosity for a 10-bp deletion (c.904-12_904-3delCTATCACCAC) in the PISD gene. The patients presented with Liberfarb syndrome, characterised by skeletal dysplasia, short stature, early-onset retinal degeneration, developmental delay, microcephaly, and hearing loss. Authors noted phenotypic overlap with another previously described case (PMID: 3561949 (1986)), prompting follow-up investigation using paraffin-embedded tissue which yielded an identical homozygous variant. Haplotype analysis indicated a founder effect between all five individuals.

PMID: 30858161 (2019) - Two sisters with progressive short stature, skeletal dysplasia, white matter abnormalities, congenital cataracts, sensorineural hearing loss, and mild global developmental delay, associated with compound heterozygous variants (c.830G>A and c.697+5G>A) in the PISD gene.

PMID: 30488656 (2019) - Two unrelated individuals with an 'unclassifiable' form of spondyloepimetaphyseal dysplasia, as well as short stature, microcephaly, mild facial dysmorphism. Vision, hearing, and psychomotor development were reported to be normal for both patients. WES identified the same homozygous missense variant (c.797G>A) in PISD in both patients. Analysis revealed a common haplotype, which indicated remote consanguinity. Supporting functional data using patient-derived fibroblasts.
Sources: Literature
Skeletal dysplasia v2.11 PLCB3 Zornitza Stark gene: PLCB3 was added
gene: PLCB3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PLCB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLCB3 were set to 29122926
Phenotypes for gene: PLCB3 were set to Spondylometaphyseal dysplasia with corneal dystrophy, MIM# 618961
Review for gene: PLCB3 was set to RED
Added comment: Single consanguineous family reported.
Sources: Literature
Skeletal dysplasia v2.11 GNPNAT1 Arina Puzriakova Classified gene: GNPNAT1 as Amber List (moderate evidence)
Skeletal dysplasia v2.11 GNPNAT1 Arina Puzriakova Added comment: Comment on list classification: Amber rating as only one family, but some supporting functional data. Additional cases required to validate pathogenicity of GNPNAT1.
Skeletal dysplasia v2.11 GNPNAT1 Arina Puzriakova Gene: gnpnat1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.10 GNPNAT1 Arina Puzriakova edited their review of gene: GNPNAT1: Changed rating: AMBER
Skeletal dysplasia v2.10 GNPNAT1 Arina Puzriakova changed review comment from: PMID: 32591345 (2020) - Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation. Additional cases required to validate pathogenicity of GNPNAT1.
Sources: Literature; to: PMID: 32591345 (2020) - Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation.
Sources: Literature
Skeletal dysplasia v2.10 GNPNAT1 Arina Puzriakova changed review comment from: PMID: 32591345 (2020) - Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation.
Sources: Literature; to: PMID: 32591345 (2020) - Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation. Additional cases required to validate pathogenicity of GNPNAT1.
Sources: Literature
Skeletal dysplasia v2.10 GNPNAT1 Arina Puzriakova gene: GNPNAT1 was added
gene: GNPNAT1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: GNPNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPNAT1 were set to 32591345
Phenotypes for gene: GNPNAT1 were set to Rhizomelic skeletal dysplasia
Review for gene: GNPNAT1 was set to RED
Added comment: PMID: 32591345 (2020) - Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation.
Sources: Literature
Skeletal dysplasia v2.9 PLEKHM1 Eleanor Williams commented on gene: PLEKHM1: Provisionally associated with ?Osteopetrosis, autosomal recessive 6 #611497 and Osteopetrosis, autosomal dominant 3 #618107 in OMIM.

2 biallelic and 2 monoallelic cases reported. Limited family segregation data and generally targeted sequencing of only a few candidate genes. A mouse model supports the role for this protein in bone re-absorption.

BIALLELIC

PMID: 17404618 - Van Wesenbeeck et al 2007 - report that loss of function variants in the PLEKHM1 gene are responsible for the osteopetrotic phenotype of the incisors absent (ia) rat. They then screened the coding sequence of the PLEKHM1 gene in 43 patients diagnosed with various forms of osteopetrosis and identified a patient with a homozygous G→A transition at position +1 of the donor splice site of intron 3. She was diagnosed with an autosomal-recessive intermediate form of the disease. Her parents, carriers of the mutation, were related to each other and were clinically normal. The oldest brother was heterozygous for the mutation and was clinically and radiologically normal. The youngest brother was homozygous for the mutation but had not yet developed clinical symptoms.

PMID: 28290981 - Moore et al 2017 - report 19 year old white male with history of fractures, as did 2 of his brothers, presenting with clinical osteopetrosis. Genetic testing using the CTGT Osteopetrosis NextGen sequencing panel, consisting of 13 genes associated with osteopetrosis, revealed 2 heterozygous missense mutations in PLEKHM1 (exon 4 and exon 7). No segregation data.

MONOALLELIC

PMID: 27291868 - Bo et al 2016 - report a middle‐aged Chinese man who presented with the typical features of osteopetrosis: fractures after minor trauma, early tooth loss, anemia, hepatosplenomegaly, and a generalized increase in BMD. A novel de novo heterozygous mutation ( c.3051_3052delCA) in the PLEKHM1 gene was identified, after initial screening of ClCN7 and TNFSF11 genes found no disease causing variants. The patient's unaffected parents and children were also screen and were not found to have the deletion.

PMID: 17997709 - Del Fattore et al 2008 - describe a new heterozygous missense mutation (R714C) in the PLEKHM1 gene in a female Italian patient with generalized osteopenia and localized osteosclerosis, with a diagnosis of osteopetrosis of the skull, However they state that it is NOT a case of osteopetrosis, because in the patient, urine CTX, a marker of in vivo bone resorption, was normal, and in vitro assays of osteoclast formation and resorptive function showed no abnormalities. She was screened for variants only in ClC‐7 and PLEKHM1. No other family members were available for analysis.

MOUSE MODEL
PMID: 27777970 - Fujiwara et al 2016 - Plekhm1-deficient mice displayed no overt abnormalities in major organs, except for an increase in trabecular bone mass. Loss of Plekhm1 increased cancellous bone mass due to decreased bone resorption without obvious defects in other tissues and organs.
Skeletal dysplasia v2.9 SOX9 Eleanor Williams commented on gene: SOX9: ESHG2020 - Poster E-PO1.34 Ledig et al Report a case of two sisters, 46XY, who are homozygous for a variant, c.1518C>G p.(Leu506Val), in SOX9. The sisters had a suspicion of non-syndromic XY DSD (disorder of sexual development) and no signs of skeletal malformations. By luciferase assay the variant reporte dhereshowed no decrease of transactivating function on Col2a1 promotor in contrast to two SOX9 mutations (c.347C>T p.(Ala116Val) and c.358C>T p.(Arg120Cys)) known to be associated with CD. The authors suggest that SOX9 variant c.1518C>G p.(Leu506Val) is a hypomorphic mutation that causes XY DSD without raising any SOX9 related skeletal phenotype.
No publication relating to this work could be found in PubMed at this time.
Skeletal dysplasia v2.9 ANO5 Zornitza Stark reviewed gene: ANO5: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32112655; Phenotypes: Gnathodiaphyseal dysplasia, MIM# 166260; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v2.9 C16orf62 Sarah Leigh Classified gene: C16orf62 as Amber List (moderate evidence)
Skeletal dysplasia v2.9 C16orf62 Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 31712251).
Skeletal dysplasia v2.9 C16orf62 Sarah Leigh Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.8 C16orf62 Sarah Leigh gene: C16orf62 was added
gene: C16orf62 was added to Skeletal dysplasia. Sources: Literature
new-gene-name tags were added to gene: C16orf62.
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 31712251
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: The HGNC approved name for this gene is: VPS35 endosomal protein sorting factor like (VPS35L)
Sources: Literature
Skeletal dysplasia v2.7 WDR34 Catherine Snow Tag new-gene-name tag was added to gene: WDR34.
Skeletal dysplasia v2.7 WDR34 Catherine Snow commented on gene: WDR34
Skeletal dysplasia v2.7 WDR60 Catherine Snow Tag new-gene-name tag was added to gene: WDR60.
Skeletal dysplasia v2.7 WDR60 Catherine Snow commented on gene: WDR60
Skeletal dysplasia v2.7 POLR1B Zornitza Stark gene: POLR1B was added
gene: POLR1B was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: POLR1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR1B were set to 31649276
Phenotypes for gene: POLR1B were set to Treacher-Collins syndrome type 4
Review for gene: POLR1B was set to GREEN
gene: POLR1B was marked as current diagnostic
Added comment: Five unrelated families and a zebrafish model, variant inherited in two of the families, once from affected parent and once from mosaic parent. Note four of the families had missense variants affecting same residue, p.Arg1003
Sources: Literature
Skeletal dysplasia v2.7 UBA2 Zornitza Stark gene: UBA2 was added
gene: UBA2 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBA2 were set to 31332306; 31587267
Phenotypes for gene: UBA2 were set to Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Review for gene: UBA2 was set to AMBER
Added comment: PMID: 31332306 - a single individual with a de novo PTC and split hand/foot malformation (SHFM). Additional two multigenic CNVs including this gene in individuals with SHFM and ectrodactyly. Authors mention an additional de novo missense but the patient didnt have SHFM, argue low penetrance PMID: 31587267 - a mother and son with aplasia cutis congenita (ACC), with a heterozygous PTC. Son also has ectrodactyly. Authors note an additional de novo missense in a patient with ACC.
Sources: Literature
Skeletal dysplasia v2.7 PKDCC Zornitza Stark gene: PKDCC was added
gene: PKDCC was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PKDCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKDCC were set to 30478137; 19097194
Phenotypes for gene: PKDCC were set to Rhizomelia; dysmorphism
Review for gene: PKDCC was set to AMBER
Added comment: Two unrelated consanguineous families reported with different homozygous variants
Pre-existing mouse model has similar phenotype
Sources: Literature
Skeletal dysplasia v2.7 NXN Ellen McDonagh Classified gene: NXN as Green List (high evidence)
Skeletal dysplasia v2.7 NXN Ellen McDonagh Added comment: Comment on list classification: Promoted to Green after expert review from Sian Ellard (by email).
Skeletal dysplasia v2.7 NXN Ellen McDonagh Gene: nxn has been classified as Green List (High Evidence).
Skeletal dysplasia v2.6 NXN Ellen McDonagh Deleted their comment
Skeletal dysplasia v2.6 NXN Ellen McDonagh Deleted their comment
Skeletal dysplasia v2.6 NXN Ellen McDonagh Deleted their comment
Skeletal dysplasia v2.6 NXN Ellen McDonagh Classified gene: NXN as Amber List (moderate evidence)
Skeletal dysplasia v2.6 NXN Ellen McDonagh Added comment: Comment on list classification: Two family reports and mouse model...should this be promoted to Green?
Skeletal dysplasia v2.6 NXN Ellen McDonagh Gene: nxn has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.6 NXN Ellen McDonagh Classified gene: NXN as Amber List (moderate evidence)
Skeletal dysplasia v2.6 NXN Ellen McDonagh Added comment: Comment on list classification: Two family reports and mouse model...should this be promoted to Green?
Skeletal dysplasia v2.6 NXN Ellen McDonagh Gene: nxn has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.5 NXN Ellen McDonagh Classified gene: NXN as Amber List (moderate evidence)
Skeletal dysplasia v2.5 NXN Ellen McDonagh Added comment: Comment on list classification: Two family reports and mouse model...should this be promoted to Green?
Skeletal dysplasia v2.5 NXN Ellen McDonagh Gene: nxn has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.5 NXN Ellen McDonagh Classified gene: NXN as Amber List (moderate evidence)
Skeletal dysplasia v2.5 NXN Ellen McDonagh Added comment: Comment on list classification: Two family reports and mouse model...should this be promoted to Green?
Skeletal dysplasia v2.5 NXN Ellen McDonagh Gene: nxn has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.4 NXN Ellen McDonagh changed review comment from: Gene suggested by Sian Ellard (Royal Devon & Exeter NHS Foundation Trust, South West Genomic Laboratory Hub) to be added to this panel. PMID: 29276006 reports three individuals from two families with biallelic vairants in this gene that co-segregate with the disease. All three patients have typical facial characteristics of Robinow syndrome, mesomelia, brachydactyly, and broad thumbs/toes NXN knockout mice have craniofacial defects which is hypothesized to be caused by abnormal Wnt/Beta-catenin signalling.
Sources: Literature, Expert Review; to: Gene suggested by Sian Ellard (Royal Devon & Exeter NHS Foundation Trust, South West Genomic Laboratory Hub) to be added to this panel. PMID: 29276006 reports three individuals from two families with biallelic vairants in this gene that co-segregate with the disease. All three patients have typical facial characteristics of Robinow syndrome, mesomelia, brachydactyly, and broad thumbs/toes. NXN knockout mice have craniofacial defects which is hypothesized to be caused by abnormal Wnt/Beta-catenin signalling.
Skeletal dysplasia v2.4 NXN Ellen McDonagh gene: NXN was added
gene: NXN was added to Skeletal dysplasia. Sources: Literature,Expert Review
Mode of inheritance for gene: NXN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NXN were set to 29276006
Phenotypes for gene: NXN were set to Robinow syndrome, autosomal recessive 2 618529
Review for gene: NXN was set to AMBER
Added comment: Gene suggested by Sian Ellard (Royal Devon & Exeter NHS Foundation Trust, South West Genomic Laboratory Hub) to be added to this panel. PMID: 29276006 reports three individuals from two families with biallelic vairants in this gene that co-segregate with the disease. All three patients have typical facial characteristics of Robinow syndrome, mesomelia, brachydactyly, and broad thumbs/toes NXN knockout mice have craniofacial defects which is hypothesized to be caused by abnormal Wnt/Beta-catenin signalling.
Sources: Literature, Expert Review
Skeletal dysplasia v2.3 CSGALNACT1 Tracy Lester gene: CSGALNACT1 was added
gene: CSGALNACT1 was added to Skeletal dysplasia. Sources: Expert Review
Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSGALNACT1 were set to 27599773; 31325655
Phenotypes for gene: CSGALNACT1 were set to Desbuquois dysplasia with mild joint laxity; non-proportionate short stature
Added comment: Desbuquois dysplasia with mild joint laxity - 2 cases reported plus a mouse model that recapitulates the phenotype: green gene for skeletal dysplasia panel
Sources: Expert Review
Skeletal dysplasia v2.3 NPR3 Ian Berry gene: NPR3 was added
gene: NPR3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: NPR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPR3 were set to PMID: 30032985; 10468599
Phenotypes for gene: NPR3 were set to Tall stature; arachnodactyly; extra epiphyses; aortic dilatation
Penetrance for gene: NPR3 were set to unknown
Review for gene: NPR3 was set to GREEN
gene: NPR3 was marked as current diagnostic
Added comment: 4 individuals in 3 families reported with striking phenotypic similarity.
Functional evidence compelling.
Mouse model recapitulates phenotype (including skeletal features).
Sources: Literature
Skeletal dysplasia v2.3 TBXAS1 Tracy Lester edited their review of gene: TBXAS1: Added comment: Variants in the AD form are associated with a bleeding disorder - no evidence of skeletal dysplasia in these patients. Mode of inheritance should just be biallelic for the skeletal dysplasia panel.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.3 Eleanor Williams Panel version has been signed off
Skeletal dysplasia v2.0 SCUBE3 Eleanor Williams changed review comment from: A variant in this gene has been found in a 100K proband as potentially being the cause of a skeletal dysplasia.; to: A variant in this gene has been found in a 100K proband as potentially being the cause of a skeletal dysplasia.
Skeletal dysplasia v2.0 SCUBE3 Eleanor Williams commented on gene: SCUBE3
Skeletal dysplasia v2.0 SCUBE3 Zerin Hyder gene: SCUBE3 was added
gene: SCUBE3 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: SCUBE3 was set to BIALLELIC, autosomal or pseudoautosomal
Penetrance for gene: SCUBE3 were set to unknown
Skeletal dysplasia v2.0 FAM46A Louise Daugherty commented on gene: FAM46A
Skeletal dysplasia v2.0 FAM46A Louise Daugherty Tag new-gene-name tag was added to gene: FAM46A.
Skeletal dysplasia v2.0 Eleanor Williams promoted panel to version 2.0
Skeletal dysplasia v1.343 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Skeletal dysplasia v1.342 TTC8 Eleanor Williams Classified gene: TTC8 as Green List (high evidence)
Skeletal dysplasia v1.342 TTC8 Eleanor Williams Gene: ttc8 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.341 ALX1 Eleanor Williams Classified gene: ALX1 as Green List (high evidence)
Skeletal dysplasia v1.341 ALX1 Eleanor Williams Added comment: Comment on list classification: Rating green due to association with FRONTONASAL DYSPLASIA TYPE 3. Other Frontonasal dysplasia genes ALX3 and ALX4 have been included on this panel. Including on the panel following the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.341 ALX1 Eleanor Williams Gene: alx1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.340 ALX1 Eleanor Williams commented on gene: ALX1: This gene is provisionally associated with ?Frontonasal dysplasia 3 (#613456) in OMIM. Has a confirmed association with FRONTONASAL DYSPLASIA TYPE 3 in Gene2Phenotype.

PMID: 20451171 - Uz et al. (2010) - 2 families presenting with autosomal-recessive frontonasal dysplasia (FND) characterized by bilateral extreme microphthalmia, bilateral oblique facial cleft, complete cleft palate, hypertelorism, wide nasal bridge with hypoplasia of the ala nasi, and low-set, posteriorly rotated ears in two distinct families. In one family they found a three siblings were affected, and CNV analysis of the critical region showed a homozygous 3.7 Mb deletion containing the ALX1 (CART1) gene. In the second family a homozygous donor-splice-site mutation (c.531+1G > A) in the ALX1 gene was found.

PMID: 27324866 - Ullah et al 2017 - report a consanguineous family from Pakistan with four individuals presenting a milder form of Frontonasal dysplasia. Using exome sequencing, a homozygous splice acceptor site variant has been identified in the ALX1 gene. The affected individuals had ptosis (drooping upper eyelid), small and upslanting palpebral fissures, blepharophimosis, broad nasal root, wide prominent nasal bridge, short and wide nasal ridge, broad columella, smooth philtrum, and mouth protrusion accompanied by teeth protrusion NOTE: no clefting reported in the individuals from this family.

PMID: 26610632 - Lyons et al 2015 - The “Contemporary” Burmese lineage of cats has a more brachycephalic head type. Offspring from “Contemporary” style mating produced a craniofacial defect in 25% of offspring (Noden and Evans, 1986; Sponenberg and Graf-Webster, 1986). The abnormality is characterized by agenesis of all derivatives of the medial nasal prominence; lateral duplication of most derivatives of the maxillary process; including the canine teeth and whiskers fields; telencephalic meningoencephalocele; and secondary ocular degeneration . The midline facial defect is autosomal recessive, however, carriers of the mutation are more brachycephalic individuals than wildtype, The entire ALX1 CDS sequence was analyzed in ten cats, including five affected Burmese and five controls. A 12 bp deletion (c.496delCTCTCAGGACTG) was identified in the coding region of ALX1. All the unaffected cats in the pedigree were confirmed to be homozygous wild-type or carrier of the 12 bp deletion while all the affected cats were homozygous for the identified variant. The average CDS homology between human and cat is 93.8% and the protein identity is 97.5%.
Skeletal dysplasia v1.340 WDPCP Eleanor Williams Classified gene: WDPCP as Green List (high evidence)
Skeletal dysplasia v1.340 WDPCP Eleanor Williams Added comment: Comment on list classification: Making this gene green as it is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.340 WDPCP Eleanor Williams Gene: wdpcp has been classified as Green List (High Evidence).
Skeletal dysplasia v1.339 WDPCP Eleanor Williams Phenotypes for gene: WDPCP were changed from to ?Congenital heart defects, hamartomas of tongue, and polysyndactyly 217085; ?Bardet-Biedl syndrome 15, 615992
Skeletal dysplasia v1.338 WDPCP Eleanor Williams Publications for gene: WDPCP were set to
Skeletal dysplasia v1.337 WDPCP Eleanor Williams Mode of inheritance for gene: WDPCP was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.336 TTC8 Eleanor Williams Classified gene: TTC8 as Red List (low evidence)
Skeletal dysplasia v1.336 TTC8 Eleanor Williams Added comment: Comment on list classification: Making this gene green as it is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.336 TTC8 Eleanor Williams Gene: ttc8 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.335 TTC8 Eleanor Williams Phenotypes for gene: TTC8 were changed from to Polydactyly; Bardet-Biedl syndrome 8, 615985
Skeletal dysplasia v1.334 TTC8 Eleanor Williams Mode of inheritance for gene: TTC8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.333 TRIM32 Eleanor Williams Classified gene: TRIM32 as Red List (low evidence)
Skeletal dysplasia v1.333 TRIM32 Eleanor Williams Added comment: Comment on list classification: Keeping this gene red as it is is red on the GMS Bardet Biedl syndrome panel (v1.0). Also associated with Muscular dystrophy, limb-girdle, autosomal recessive 8 but no skeletal phenotype is present in this disorder.
Skeletal dysplasia v1.333 TRIM32 Eleanor Williams Gene: trim32 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.332 TRIM32 Eleanor Williams Phenotypes for gene: TRIM32 were changed from to Bardet-Biedl syndrome 11, 615988; Polydactyly
Skeletal dysplasia v1.331 SDCCAG8 Eleanor Williams Classified gene: SDCCAG8 as Red List (low evidence)
Skeletal dysplasia v1.331 SDCCAG8 Eleanor Williams Added comment: Comment on list classification: This gene is a Bardet-Biedl syndrome gene but polydactyly is not part of the phenotype - see clinical features listed in OMIM https://omim.org/entry/615993. Therefore keeping this gene red on the skeletal dysplasia panel.
Skeletal dysplasia v1.331 SDCCAG8 Eleanor Williams Gene: sdccag8 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.330 SDCCAG8 Eleanor Williams Phenotypes for gene: SDCCAG8 were changed from Senior-Loken syndrome 7, 613615; Bardet-Biedl syndrome 16, 615993 to Bardet-Biedl syndrome 16, 615993
Skeletal dysplasia v1.329 SDCCAG8 Eleanor Williams Phenotypes for gene: SDCCAG8 were changed from to Senior-Loken syndrome 7, 613615; Bardet-Biedl syndrome 16, 615993
Skeletal dysplasia v1.328 SDCCAG8 Eleanor Williams Mode of inheritance for gene: SDCCAG8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.327 MKKS Eleanor Williams Classified gene: MKKS as Green List (high evidence)
Skeletal dysplasia v1.327 MKKS Eleanor Williams Added comment: Comment on list classification: Making this gene green as it is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.327 MKKS Eleanor Williams Gene: mkks has been classified as Green List (High Evidence).
Skeletal dysplasia v1.326 MKKS Eleanor Williams Phenotypes for gene: MKKS were changed from to Polydactyly; Bardet-Biedl syndrome 6, 605231; McKusick-Kaufman syndrome, 236700
Skeletal dysplasia v1.325 MKKS Eleanor Williams Mode of inheritance for gene: MKKS was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.324 CCDC28B Eleanor Williams Classified gene: CCDC28B as Red List (low evidence)
Skeletal dysplasia v1.324 CCDC28B Eleanor Williams Added comment: Comment on list classification: Keeping this gene on the panel as red as it is red on the GMS Bardet Biedl syndrome panel (v1.0). Modifier gene.
Skeletal dysplasia v1.324 CCDC28B Eleanor Williams Gene: ccdc28b has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.323 CCDC28B Eleanor Williams Mode of inheritance for gene: CCDC28B was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.322 CCDC28B Eleanor Williams Publications for gene: CCDC28B were set to
Skeletal dysplasia v1.321 CCDC28B Eleanor Williams Phenotypes for gene: CCDC28B were changed from to {Bardet-Biedl syndrome 1, modifier of}, 209900
Skeletal dysplasia v1.320 BBS9 Eleanor Williams Classified gene: BBS9 as Green List (high evidence)
Skeletal dysplasia v1.320 BBS9 Eleanor Williams Added comment: Comment on list classification: Making this gene green as it is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.320 BBS9 Eleanor Williams Gene: bbs9 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.319 BBS9 Eleanor Williams Phenotypes for gene: BBS9 were changed from to Polydactyly; Bardet Biedl syndrome 9, 615986
Skeletal dysplasia v1.318 BBS9 Eleanor Williams Mode of inheritance for gene: BBS9 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.317 BBS7 Eleanor Williams Classified gene: BBS7 as Green List (high evidence)
Skeletal dysplasia v1.317 BBS7 Eleanor Williams Gene: bbs7 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.316 BBS7 Eleanor Williams Classified gene: BBS7 as Red List (low evidence)
Skeletal dysplasia v1.316 BBS7 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.316 BBS7 Eleanor Williams Gene: bbs7 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.315 BBS7 Eleanor Williams Phenotypes for gene: BBS7 were changed from to Polydactyly; Bardet-Biedl syndrome 7, 615984
Skeletal dysplasia v1.314 BBS7 Eleanor Williams Mode of inheritance for gene: BBS7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.313 BBS5 Eleanor Williams Classified gene: BBS5 as Green List (high evidence)
Skeletal dysplasia v1.313 BBS5 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.313 BBS5 Eleanor Williams Gene: bbs5 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.312 BBS5 Eleanor Williams Phenotypes for gene: BBS5 were changed from to Polydactyly; Bardet Biedl syndrome 5, 615983
Skeletal dysplasia v1.311 BBS5 Eleanor Williams Mode of inheritance for gene: BBS5 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.310 BBS4 Eleanor Williams Classified gene: BBS4 as Green List (high evidence)
Skeletal dysplasia v1.310 BBS4 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.310 BBS4 Eleanor Williams Gene: bbs4 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.309 BBS4 Eleanor Williams Phenotypes for gene: BBS4 were changed from to Polydactyly; Bardet-Biedl syndrome 4, 615982
Skeletal dysplasia v1.308 BBS4 Eleanor Williams Mode of inheritance for gene: BBS4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.307 BBS2 Eleanor Williams Classified gene: BBS2 as Green List (high evidence)
Skeletal dysplasia v1.307 BBS2 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.307 BBS2 Eleanor Williams Gene: bbs2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.306 BBS2 Eleanor Williams Phenotypes for gene: BBS2 were changed from to Polydactyly; Bardet-Biedl syndrome 2, 615981
Skeletal dysplasia v1.305 BBS2 Eleanor Williams Mode of inheritance for gene: BBS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.304 BBS12 Eleanor Williams Classified gene: BBS12 as Green List (high evidence)
Skeletal dysplasia v1.304 BBS12 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.304 BBS12 Eleanor Williams Gene: bbs12 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.303 BBS12 Eleanor Williams Phenotypes for gene: BBS12 were changed from to Polydactyly; Bardet Biedl syndrome 12, 615989
Skeletal dysplasia v1.302 BBS12 Eleanor Williams Mode of inheritance for gene: BBS12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.301 BBS10 Eleanor Williams Classified gene: BBS10 as Green List (high evidence)
Skeletal dysplasia v1.301 BBS10 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.301 BBS10 Eleanor Williams Gene: bbs10 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.300 BBS10 Eleanor Williams Phenotypes for gene: BBS10 were changed from to Polydactyly; Bardet Biedl syndrome 10, 615987
Skeletal dysplasia v1.299 BBS10 Eleanor Williams Mode of inheritance for gene: BBS10 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.298 BBS1 Eleanor Williams Classified gene: BBS1 as Green List (high evidence)
Skeletal dysplasia v1.298 BBS1 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.298 BBS1 Eleanor Williams Gene: bbs1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.297 BBS1 Eleanor Williams Phenotypes for gene: BBS1 were changed from to Polydactyly; Bardet-Biedl syndrome 1 209900
Skeletal dysplasia v1.297 BBS1 Eleanor Williams Publications for gene: BBS1 were set to
Skeletal dysplasia v1.296 BBS1 Eleanor Williams Mode of inheritance for gene: BBS1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.295 ARL6 Eleanor Williams Classified gene: ARL6 as Green List (high evidence)
Skeletal dysplasia v1.295 ARL6 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.295 ARL6 Eleanor Williams Gene: arl6 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.294 ARL6 Eleanor Williams Phenotypes for gene: ARL6 were changed from to Polydactyly; Bardet-Biedl syndrome 3 600151
Skeletal dysplasia v1.294 ARL6 Eleanor Williams Publications for gene: ARL6 were set to
Skeletal dysplasia v1.293 ARL6 Eleanor Williams Mode of inheritance for gene: ARL6 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.292 SHOX Eleanor Williams Added comment: Comment on mode of inheritance: Monoallelic cases tend to be milder e.g. familial short stature / Leri-Weill, whereas biallelic are more severe (Langer mesomelic dysplasia).
Skeletal dysplasia v1.292 SHOX Eleanor Williams Mode of inheritance for gene: SHOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Skeletal dysplasia v1.291 Eleanor Williams List of related panels changed from Unexplained skeletal dysplasia; Skeletal dysplasia to Unexplained skeletal dysplasia; Skeletal dysplasia; R104
Skeletal dysplasia v1.290 WRN Eleanor Williams changed review comment from: Comment on list classification: Keeping red for now. Associated with Werner syndrome with Osteoporosis and slender limbs listed as clinical features in OMIM. Short stature.; to: Comment on list classification: Keeping red for now. Associated with Werner syndrome with Osteoporosis and slender limbs listed as clinical features in OMIM. Short stature. But need confirmation that this is considered strong enough a skeletal dysplasia phenotype before promoting to green.
Skeletal dysplasia v1.290 WRN Eleanor Williams Classified gene: WRN as Red List (low evidence)
Skeletal dysplasia v1.290 WRN Eleanor Williams Added comment: Comment on list classification: Keeping red for now. Associated with Werner syndrome with Osteoporosis and slender limbs listed as clinical features in OMIM. Short stature.
Skeletal dysplasia v1.290 WRN Eleanor Williams Gene: wrn has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.289 TGDS Eleanor Williams Classified gene: TGDS as Red List (low evidence)
Skeletal dysplasia v1.289 TGDS Eleanor Williams Added comment: Comment on list classification: Leaving red for now. Associated with Catel-Manzke syndrome. Mainly limb phenotype.
Skeletal dysplasia v1.289 TGDS Eleanor Williams Gene: tgds has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.288 OAT Eleanor Williams Classified gene: OAT as Red List (low evidence)
Skeletal dysplasia v1.288 OAT Eleanor Williams Added comment: Comment on list classification: Leaving red for now as no skeletal involvement found in publications found to date.
Skeletal dysplasia v1.288 OAT Eleanor Williams Gene: oat has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.287 IDH2 Eleanor Williams Classified gene: IDH2 as Red List (low evidence)
Skeletal dysplasia v1.287 IDH2 Eleanor Williams Added comment: Comment on list classification: Keeping red for now. Associated with D-2-hydroxyglutaric aciduria 2 in OMIM but no skeletal phenotype. Also associated with somatic mosaic variants in patients with multiple enchondromas (Ollier disease) which can result in a skeletal phenotype.
Skeletal dysplasia v1.287 IDH2 Eleanor Williams Gene: idh2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.286 EP300 Eleanor Williams Classified gene: EP300 as Red List (low evidence)
Skeletal dysplasia v1.286 EP300 Eleanor Williams Added comment: Comment on list classification: Keeping red for now. Associated with Rubinstein-Taybi syndrome. Mainly minor digital phenotype
Skeletal dysplasia v1.286 EP300 Eleanor Williams Gene: ep300 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.285 CKAP2L Eleanor Williams Classified gene: CKAP2L as Red List (low evidence)
Skeletal dysplasia v1.285 CKAP2L Eleanor Williams Added comment: Comment on list classification: Keeping red for now. Associated with Filippi syndrome in OMIM. Mainly a digital phenotype.
Skeletal dysplasia v1.285 CKAP2L Eleanor Williams Gene: ckap2l has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.284 ARID1B Eleanor Williams Classified gene: ARID1B as Red List (low evidence)
Skeletal dysplasia v1.284 ARID1B Eleanor Williams Added comment: Comment on list classification: Keeping red for now. Associated with Coffin-Siris syndrome 1 in OMIM. Clinical features list short stature in some patients, but mainly a limb phenotype including hypoplastic digits and nails. Not classical for a skeletal panel.
Skeletal dysplasia v1.284 ARID1B Eleanor Williams Gene: arid1b has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.283 AKT1 Eleanor Williams Classified gene: AKT1 as Red List (low evidence)
Skeletal dysplasia v1.283 AKT1 Eleanor Williams Added comment: Comment on list classification: Keeping red for now. Associated with Proteus syndrome, somatic in OMIM, more consistent with segmental overgrowth, a mosaic disorder
Skeletal dysplasia v1.283 AKT1 Eleanor Williams Gene: akt1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.282 ABL1 Eleanor Williams Classified gene: ABL1 as Amber List (moderate evidence)
Skeletal dysplasia v1.282 ABL1 Eleanor Williams Added comment: Comment on list classification: Leaving this gene as amber just now. Question as to whether this is considered a skeletal dysplasia. The broader skeletal manifestations (scoliosis / pectus) are classically thought of as part of the Marfan / FTAAD spectrum rather than a skeletal dysplasia.
Skeletal dysplasia v1.282 ABL1 Eleanor Williams Gene: abl1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.281 DPAGT1 Eleanor Williams Classified gene: DPAGT1 as Green List (high evidence)
Skeletal dysplasia v1.281 DPAGT1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. It is green on the Congenital disorders of glycosylation panel (panel ID:25, version 1.32). Decision agreed with Prof Lyn Chitty.
Skeletal dysplasia v1.281 DPAGT1 Eleanor Williams Gene: dpagt1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.280 DPAGT1 Eleanor Williams Publications for gene: DPAGT1 were set to 12872255; 22304930
Skeletal dysplasia v1.279 DPAGT1 Eleanor Williams gene: DPAGT1 was added
gene: DPAGT1 was added to Skeletal dysplasia. Sources: Expert list
Mode of inheritance for gene: DPAGT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPAGT1 were set to 12872255; 22304930
Phenotypes for gene: DPAGT1 were set to Congenital disorder of glycosylation, type Ij 608093; Myasthenic syndrome, congenital, 13, with tubular aggregates 614750; UDP-GlcNAc:Dol-P-GlcNac-P transferase deficiency (Disorders of protein N-glycosylation)
Review for gene: DPAGT1 was set to GREEN
Added comment: Adding gene to the panel from suggestion from Rhoda Akilapa. Skeletal anomalies reported including Rocker bottom feet, Bell-shaped chest, Multiple contractures, campodactily in hands,
Dorsal kyphosis, valgum feet, articular hyperlaxity (PMID: 30653653)
Sources: Expert list
Skeletal dysplasia v1.278 B3GLCT Eleanor Williams Classified gene: B3GLCT as Green List (high evidence)
Skeletal dysplasia v1.278 B3GLCT Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. It is green on the Congenital disorders of glycosylation panel (panel ID:25, version 1.32). Decision agreed with Prof Lyn Chitty.
Skeletal dysplasia v1.278 B3GLCT Eleanor Williams Gene: b3glct has been classified as Green List (High Evidence).
Skeletal dysplasia v1.277 B3GLCT Eleanor Williams gene: B3GLCT was added
gene: B3GLCT was added to Skeletal dysplasia. Sources: Expert Review
Mode of inheritance for gene: B3GLCT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GLCT were set to 16909395; 23889335
Phenotypes for gene: B3GLCT were set to Peters-plus syndrome 261540; O-fucose-specific beta-1,3-N-glucosyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies)
Review for gene: B3GLCT was set to GREEN
Added comment: Adding gene to the panel from suggestion from Rhoda Akilapa. Growth retardation, short stature, and brachydactyly reported.
Sources: Expert Review
Skeletal dysplasia v1.276 SLC35C1 Eleanor Williams Classified gene: SLC35C1 as Green List (high evidence)
Skeletal dysplasia v1.276 SLC35C1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. It is green on the Congenital disorders of glycosylation panel (panel ID:25, version 1.32). Decision agreed with Prof Lyn Chitty.
Skeletal dysplasia v1.276 SLC35C1 Eleanor Williams Gene: slc35c1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.275 SLC35C1 Eleanor Williams gene: SLC35C1 was added
gene: SLC35C1 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: SLC35C1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35C1 were set to 11326280; 12476046
Phenotypes for gene: SLC35C1 were set to Congenital disorder of glycosylation, type IIc 266265; GDP-fucose transporter deficiency (Disorders of multiple glycosylation and other glycosylation pathways)
Added comment: Adding gene to the panel from suggestion from Rhoda Akilapa. Dwarfism reported
Sources: Other
Skeletal dysplasia v1.274 SLC34A1 Eleanor Williams Classified gene: SLC34A1 as Green List (high evidence)
Skeletal dysplasia v1.274 SLC34A1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Including genes that are green on the Hypophosphataemia or rickets panel (panel ID:482, version 2.1) as green on the Skeletal dysplasia panel on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.274 SLC34A1 Eleanor Williams Gene: slc34a1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.273 SLC34A1 Eleanor Williams gene: SLC34A1 was added
gene: SLC34A1 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: SLC34A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC34A1 were set to 12324554; 9560283; 25050900
Phenotypes for gene: SLC34A1 were set to Nephrolithiasis/osteoporosis, hypophosphatemic, 1, 612286
Review for gene: SLC34A1 was set to GREEN
Added comment: Adding genes that are green on the Hypophosphataemia or rickets panel
Sources: Other
Skeletal dysplasia v1.272 CYP2R1 Eleanor Williams Classified gene: CYP2R1 as Green List (high evidence)
Skeletal dysplasia v1.272 CYP2R1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Including genes that are green on the Hypophosphataemia or rickets panel (panel ID:482, version 2.1) as green on the Skeletal dysplasia panel on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.272 CYP2R1 Eleanor Williams Gene: cyp2r1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.271 CYP2R1 Eleanor Williams gene: CYP2R1 was added
gene: CYP2R1 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: CYP2R1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP2R1 were set to 22855339; 15128933; 28548312; 25942481
Phenotypes for gene: CYP2R1 were set to Rickets due to defect in vitamin D 25-hydroxylation, 600081
Review for gene: CYP2R1 was set to GREEN
Added comment: Adding genes that are green on the Hypophosphataemia or rickets panel
Sources: Other
Skeletal dysplasia v1.270 VDR Eleanor Williams Classified gene: VDR as Green List (high evidence)
Skeletal dysplasia v1.270 VDR Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Including genes that are green on the Hypophosphataemia or rickets panel (panel ID:482, version 2.1) as green on the Skeletal dysplasia panel on the advice of Prof Lyn Chitty
Skeletal dysplasia v1.270 VDR Eleanor Williams Gene: vdr has been classified as Green List (High Evidence).
Skeletal dysplasia v1.269 VDR Eleanor Williams Phenotypes for gene: VDR were changed from to Rickets, vitamin D-resistant, type IIA, 277440
Skeletal dysplasia v1.268 VDR Eleanor Williams Mode of inheritance for gene: VDR was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.267 FAM46A Eleanor Williams Classified gene: FAM46A as Green List (high evidence)
Skeletal dysplasia v1.267 FAM46A Eleanor Williams Gene: fam46a has been classified as Green List (High Evidence).
Skeletal dysplasia v1.266 TAPT1 Eleanor Williams Classified gene: TAPT1 as Green List (high evidence)
Skeletal dysplasia v1.266 TAPT1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.266 TAPT1 Eleanor Williams Gene: tapt1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.265 TAPT1 Eleanor Williams Publications for gene: TAPT1 were set to PMID:26365339
Skeletal dysplasia v1.264 SPARC Eleanor Williams Classified gene: SPARC as Green List (high evidence)
Skeletal dysplasia v1.264 SPARC Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.264 SPARC Eleanor Williams Gene: sparc has been classified as Green List (High Evidence).
Skeletal dysplasia v1.263 SPARC Eleanor Williams Publications for gene: SPARC were set to
Skeletal dysplasia v1.262 SP7 Eleanor Williams Classified gene: SP7 as Green List (high evidence)
Skeletal dysplasia v1.262 SP7 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.262 SP7 Eleanor Williams Gene: sp7 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.261 NBAS Eleanor Williams Classified gene: NBAS as Green List (high evidence)
Skeletal dysplasia v1.261 NBAS Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.261 NBAS Eleanor Williams Gene: nbas has been classified as Green List (High Evidence).
Skeletal dysplasia v1.260 NBAS Eleanor Williams Publications for gene: NBAS were set to
Skeletal dysplasia v1.259 NBAS Eleanor Williams Mode of inheritance for gene: NBAS was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.258 FAM46A Eleanor Williams Classified gene: FAM46A as Red List (low evidence)
Skeletal dysplasia v1.258 FAM46A Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.258 FAM46A Eleanor Williams Gene: fam46a has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.257 FAM46A Eleanor Williams gene: FAM46A was added
gene: FAM46A was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: FAM46A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM46A were set to 29358272
Phenotypes for gene: FAM46A were set to Osteogenesis imperfecta, type XVIII 617952
Review for gene: FAM46A was set to GREEN
Added comment: Adding gene to panel as it is green on the Osteogenesis imperfecta panel.
Sources: Other
Skeletal dysplasia v1.256 CREB3L1 Eleanor Williams changed review comment from: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Lyn Chitty.; to: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.256 DSPP Eleanor Williams changed review comment from: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Lyn Chitty.; to: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.256 DSPP Eleanor Williams Classified gene: DSPP as Green List (high evidence)
Skeletal dysplasia v1.256 DSPP Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Lyn Chitty.
Skeletal dysplasia v1.256 DSPP Eleanor Williams Gene: dspp has been classified as Green List (High Evidence).
Skeletal dysplasia v1.255 CREB3L1 Eleanor Williams Classified gene: CREB3L1 as Green List (high evidence)
Skeletal dysplasia v1.255 CREB3L1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Including genes that are green on the Osteogenesis imperfecta panel (panel ID:196, version 2.0) as green on the Skeletal dysplasia panel on the advice of Lyn Chitty.
Skeletal dysplasia v1.255 CREB3L1 Eleanor Williams Gene: creb3l1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.254 PAX3 Eleanor Williams Classified gene: PAX3 as Green List (high evidence)
Skeletal dysplasia v1.254 PAX3 Eleanor Williams Added comment: Comment on list classification: Changing the rating from red to green as there is evidence for association with cranofacial and limb phenotype.
Skeletal dysplasia v1.254 PAX3 Eleanor Williams Gene: pax3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.253 PAX3 Eleanor Williams Publications for gene: PAX3 were set to
Skeletal dysplasia v1.252 PAX3 Eleanor Williams Phenotypes for gene: PAX3 were changed from Craniofacial-Deafness-Hand Syndrome to Craniofacial-deafness-hand syndrome, 122880; Waardenburg syndrome, type 1, 193500; Waardenburg syndrome, type 3, 148820
Skeletal dysplasia v1.251 PAX3 Eleanor Williams Added comment: Comment on mode of inheritance: Waardenburg syndrome, type 3 is both AD and AR in OMIM.
Skeletal dysplasia v1.251 PAX3 Eleanor Williams Mode of inheritance for gene: PAX3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.250 PAX3 Eleanor Williams edited their review of gene: PAX3: Added comment: Comment from Tracy Lester - PAX3 should be made green on the skeletal dysplasia panel in the absence of any other relevant panel in the test directory. It is currently red on the Craniosynostosis panel.; Changed rating: GREEN
Skeletal dysplasia v1.250 PAX3 Eleanor Williams commented on gene: PAX3
Skeletal dysplasia v1.250 IL11RA Eleanor Williams commented on gene: IL11RA: Comment from Tracy Lester - IL11RA should stay on the skeletal dysplasia panel in the absence of a specific craniofacial panel. Some patients also display minor digit anomalies, such as syndactyly and/or clinodactyly. Cases can have midface hypoplasia and other craniofacial signs without clinical CSS.
Skeletal dysplasia v1.250 TGFBR1 Eleanor Williams changed review comment from: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester). It is green on the Craniosynostosis and Ehlers Danlos panels.; to: Comment on list classification: Suggested by Rhoda Akilapa for removal. Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester). It is green on the Craniosynostosis and Ehlers Danlos panels.
Skeletal dysplasia v1.250 IGF1R Eleanor Williams Classified gene: IGF1R as No list
Skeletal dysplasia v1.250 IGF1R Eleanor Williams Added comment: Comment on list classification: Suggested by Rhoda Akilapa for removal. Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester) that there is no major skeletal involvement. It is green on microcephaly and growth failure panels.
Skeletal dysplasia v1.250 IGF1R Eleanor Williams Gene: igf1r has been removed from the panel.
Skeletal dysplasia v1.249 EFNB1 Eleanor Williams Classified gene: EFNB1 as No list
Skeletal dysplasia v1.249 EFNB1 Eleanor Williams Added comment: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester) that it is a predominantly craniosynostosis phenotype. It is green on the Craniosynostosis panel.
Skeletal dysplasia v1.249 EFNB1 Eleanor Williams Gene: efnb1 has been removed from the panel.
Skeletal dysplasia v1.248 ZIC1 Eleanor Williams Classified gene: ZIC1 as No list
Skeletal dysplasia v1.248 ZIC1 Eleanor Williams Added comment: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester) that there is no major skeletal involvement. It is green on the Craniosynostosis panel.
Skeletal dysplasia v1.248 ZIC1 Eleanor Williams Gene: zic1 has been removed from the panel.
Skeletal dysplasia v1.247 TGFBR1 Eleanor Williams Classified gene: TGFBR1 as No list
Skeletal dysplasia v1.247 TGFBR1 Eleanor Williams Added comment: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester). It is green on the Craniosynostosis and Ehlers Danlos panels.
Skeletal dysplasia v1.247 TGFBR1 Eleanor Williams Gene: tgfbr1 has been removed from the panel.
Skeletal dysplasia v1.246 TCOF1 Eleanor Williams commented on gene: TCOF1: Comment from Tracy Lester - TCOF1 should stay on the skeletal dysplasia panel in the absence of a specific craniofacial panel. It is currently red on the Craniosynostosis panel (https://panelapp.genomicsengland.co.uk/panels/168/gene/TCOF1/)
Skeletal dysplasia v1.246 TCF12 Eleanor Williams Classified gene: TCF12 as No list
Skeletal dysplasia v1.246 TCF12 Eleanor Williams Added comment: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester) that there is no major skeletal involvement. It is green on the Craniosynostosis panel.
Skeletal dysplasia v1.246 TCF12 Eleanor Williams Gene: tcf12 has been removed from the panel.
Skeletal dysplasia v1.245 KAT6A Eleanor Williams Classified gene: KAT6A as No list
Skeletal dysplasia v1.245 KAT6A Eleanor Williams Added comment: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester) that there is no major skeletal involvement. It is green on the Craniosynostosis panel.
Skeletal dysplasia v1.245 KAT6A Eleanor Williams Gene: kat6a has been removed from the panel.
Skeletal dysplasia v1.244 ALX4 Eleanor Williams commented on gene: ALX4: Comment from Tracy Lester - ALX4 should stay on the skeletal dysplasia panel in the absence of a specific craniofacial panel. It is currently green on the Craniosynostosis panel because GOF variants can have a craniosynostosis phenotype (https://panelapp.genomicsengland.co.uk/panels/168/gene/ALX4/).
Skeletal dysplasia v1.244 ALX1 Eleanor Williams commented on gene: ALX1: Comment from Tracy Lester - ALX1 should stay on the skeletal dysplasia panel in the absence of a specific craniofacial panel. It is currently red on the Craniosynostosis panel (https://panelapp.genomicsengland.co.uk/panels/168/gene/ALX1/)
Skeletal dysplasia v1.244 ALX3 Eleanor Williams commented on gene: ALX3: Comment from Tracy Lester - ALX3 should stay on the skeletal dysplasia panel in the absence of a specific craniofacial panel. It is currently red on the Craniosynostosis panel (https://panelapp.genomicsengland.co.uk/panels/168/gene/ALX3/)
Skeletal dysplasia v1.244 LMBR1 Eleanor Williams commented on gene: LMBR1: Reported microduplications in LMBR1 associated with Laurin-Sandrow syndrome are in the SHH regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene. Duplications are >10kb and therefore the current pipeline should report these as CNVs within a green gene.
Skeletal dysplasia v1.244 RAD21 Eleanor Williams changed review comment from: Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects (2 cases). ; to: Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects.
Skeletal dysplasia v1.244 RAD21 Eleanor Williams changed review comment from: Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects (2 cases). Other cases of deletions covering this gene and a similar phenotype are also reported.; to: Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects (2 cases).
Skeletal dysplasia v1.244 RAD21 Eleanor Williams changed review comment from: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects.

OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified.

Other publications with patients with Cornelia de Lange and RAD21 variants:

PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay.

PMID: 24378232 - Minor et al., 2014 - 2 patients with atypic Cornelia de Lange. Patient 1 - in frame deletion of exon 13 - presented with developmental delay, hypospadias, inguinal hernia and dysmorphic features, mild 5th finger clinodactyly. This deletion was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems.
Patient 2 - c.592_593dup frameshift mutation - presented with developmental delay, characteristic facial features, hirsutism, and hand and feet anomalies (clinodactyly, syndactyly). The mother had the same frameshift mutation showing incomplete penetrance.

PMID: 27882533 - Boyle et al., 2017 - patient with microcephaly and classical CdLS facial features with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance.

PMID: 27620904 - Martinez et al., 2017 - 92 patients recruited with syndromic intellectual disability. 1 patient identified with a variant in RAD21. A diagnosis of CdLS was made. ; to: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects.

OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short fingers (1 patient) and thin fingers (1 patient) and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21, aswell as other genes, were reported.

Other publications with patients with Cornelia de Lange and RAD21 variants but no major skeletal phenotype:

PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay.

PMID: 24378232 - Minor et al., 2014 - 2 patients with atypic Cornelia de Lange. Patient 1 - in frame deletion of exon 13 - presented with developmental delay, hypospadias, inguinal hernia and dysmorphic features, mild 5th finger clinodactyly. This deletion was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems.
Patient 2 - c.592_593dup frameshift mutation - presented with developmental delay, characteristic facial features, hirsutism, and hand and feet anomalies (clinodactyly, syndactyly). The mother had the same frameshift mutation showing incomplete penetrance.

PMID: 27882533 - Boyle et al., 2017 - patient with microcephaly and classical CdLS facial features with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance.

PMID: 27620904 - Martinez et al., 2017 - 92 patients recruited with syndromic intellectual disability. 1 patient identified with a variant in RAD21. A diagnosis of CdLS was made.
Skeletal dysplasia v1.244 TWIST2 Eleanor Williams changed review comment from: Comment on list classification: Removing this gene from the panel as the OMIM phenotypes to not have a clear skeletal phenotype.; to: Comment on list classification: Removing this gene from the panel as the OMIM associated diseases do not have a clear skeletal phenotype.
Skeletal dysplasia v1.244 SULF1 Eleanor Williams changed review comment from: Comment on list classification: Changing rating back to red. In all reported cases associated with deletions and patients with Mesomelia-synostoses syndrome both SULF1 and SLC05A1 are deleted, so better to represent this as a region.; to: Comment on list classification: Changing rating back to red. In all reported cases associated with deletions and patients with Mesomelia-synostoses syndrome both SULF1 and SLCO5A1 are deleted, so better to represent this as a region.
Skeletal dysplasia v1.244 SLCO5A1 Eleanor Williams Classified gene: SLCO5A1 as Red List (low evidence)
Skeletal dysplasia v1.244 SLCO5A1 Eleanor Williams Added comment: Comment on list classification: Changing rating back to red. In all reported cases associated with deletions and patients with Mesomelia-synostoses syndrome both SULF1 and SLCO5A1 are deleted, so better to represent this as a region
Skeletal dysplasia v1.244 SLCO5A1 Eleanor Williams Gene: slco5a1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.243 SULF1 Eleanor Williams Classified gene: SULF1 as Red List (low evidence)
Skeletal dysplasia v1.243 SULF1 Eleanor Williams Added comment: Comment on list classification: Changing rating back to red. In all reported cases associated with deletions and patients with Mesomelia-synostoses syndrome both SULF1 and SLC05A1 are deleted, so better to represent this as a region.
Skeletal dysplasia v1.243 SULF1 Eleanor Williams Gene: sulf1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.242 SULF1 Eleanor Williams changed review comment from: Not associated with any phenotype in OMIM or Gene2Phenotype.

PMID: 20602915 - Isidor et al 2010 - using whole-genome oligonucleotide array CGH, they identified an interstitial deletion at 8q13 in 5 patients from 4 unrelated families with Mesomelia-synostoses syndrome. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1 and SLCO5A1. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Codeletion of SULF1 and SLCO5A1was found in all patients, suggesting that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS.

PMID: 28328141 - Kohmoto et al 2017 - report the first Japanese case with MSS diagnosed by detecting an 8q13 deletion (581 Kb monoallelic deletion) that resulted from a unique, distant L1s‐mediated unequal NAHR event, which is different from the possible mechanisms proposed in previously reported cases. The deletion encompasses SULF1, SLCO5A1, and LINC01603. The size of the 8q13 deletion was different from those of any of the four reported deletions responsible for MSS (Isidor et al., 2010). The deletion could not be confirmed as de novo because of the unavailability of parental DNA.

PMID: 30450550 - Dardis et al 2019 - describe the first patient affected by MSS without the previously described 8q13 deletions. Patient is an 8‐year‐old 46,XY male presenting the radiological and clinical hallmarks of MSS. Microdeletions of SULF1 and SLCO5A1 genes at 8q13 were absent. Sequencing of SULF1 and SLCO5A1 found 4 polymorphisms but no pathogenic mutations. However, it was found that there was monoallelic expression of SULF1 in the patient's cells, likely leading to SULF1 haploinsufficiency. There may be either a deletion of a portion of SULF1 gene not detectable by PCR or CGH array or mutations or epigenetic alterations in sequences that contribute to the regulation of SULF1 expression.

Summary, there are 5 cases where deletions covering both SULF1 and SLCO5A1 are found in patients with MSS. There is one case of MSS in a patient with no detectable deletions of SULF1 and SLCO5A1, but with monoallelic expression of SULF1. There is no current regions curated by ClinGen that cover these genes.; to: Not associated with any phenotype in OMIM or Gene2Phenotype.

PMID: 20602915 - Isidor et al 2010 - using whole-genome oligonucleotide array CGH, they identified an interstitial deletion at 8q13 in 5 patients from 4 unrelated families with Mesomelia-synostoses syndrome. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1 and SLCO5A1. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Codeletion of SULF1 and SLCO5A1was found in all patients, suggesting that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS.

PMID: 28328141 - Kohmoto et al 2017 - report the first Japanese case with MSS diagnosed by detecting an 8q13 deletion (581 Kb monoallelic deletion) that resulted from a unique, distant L1s‐mediated unequal NAHR event, which is different from the possible mechanisms proposed in previously reported cases. The deletion encompasses SULF1, SLCO5A1, and LINC01603. The size of the 8q13 deletion was different from those of any of the four reported deletions responsible for MSS (Isidor et al., 2010). The deletion could not be confirmed as de novo because of the unavailability of parental DNA.

PMID: 30450550 - Dardis et al 2019 - describe the first patient affected by MSS without the previously described 8q13 deletions. Patient is an 8‐year‐old 46,XY male presenting the radiological and clinical hallmarks of MSS. Microdeletions of SULF1 and SLCO5A1 genes at 8q13 were absent. Sequencing of SULF1 and SLCO5A1 found 4 polymorphisms but no pathogenic mutations. However, it was found that there was monoallelic expression of SULF1 in the patient's cells, likely leading to SULF1 haploinsufficiency. There may be either a deletion of a portion of SULF1 gene not detectable by PCR or CGH array or mutations or epigenetic alterations in sequences that contribute to the regulation of SULF1 expression.

Summary, there are 5 cases where deletions covering both SULF1 and SLCO5A1 are found in patients with MSS. There is one case of MSS in a patient with no detectable deletions of SULF1 and SLCO5A1, but with monoallelic expression of SULF1. There are no current regions curated by ClinGen that cover these genes.
Skeletal dysplasia v1.242 TGDS Eleanor Williams changed review comment from: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM.

PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation
; to: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM.

PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation. 1 patient showed short toes, short humeri, short femora, 3 had clinodactyly V and 1 had brachymetacarpia and scoliosis.

PMID: 26366375 - Pferdehirt et al 2015 - describe a 12-month-old male with molecularly confirmed Catel-Manzke syndrome who presented with Pierre Robin sequence (but without cleft palate) and hyperphalangy. This patient is on the severe end of the phenotypic spectrum, presenting with respiratory complications and failure to thrive. He has a homozygous p.Ala100Ser pathogenic variant. Both parents are heterozygous for this variant.

PMID: 28422407 - Schoner et al 2017 - report on a fetus with severe heart defect, nuchal edema, talipes, Pierre-Robin sequence, and bilateral deviation and clinodactyly of the index and middle fingers. Postmortem radiographs showed hypoplasia and V-shaped displacement of the second and third proximal phalanges of both hands as well as hypoplasia of the first metatarsals and the phalangeal bones of the halluces. Two compound heterozygous mutations in TGDS were found: c.298G>T; p.(Ala100Ser) and c.895G>A; p.(Asp299Asn), located in the predicted substrate binding site of TGDS. Analyses of the parents’ blood DNA confirmed biparental inheritance.
Skeletal dysplasia v1.242 TGDS Eleanor Williams Publications for gene: TGDS were set to
Skeletal dysplasia v1.241 TGDS Eleanor Williams Mode of inheritance for gene: TGDS was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.240 TGDS Eleanor Williams changed review comment from: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM.

PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation


In 7 patients with Catel-Manzke syndrome (616145), Ehmke et al. (2014) identified homozygosity or compound heterozygosity for mutations in the TGDS gene; to: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM.

PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation
Skeletal dysplasia v1.240 SLCO5A1 Eleanor Williams Tag currently-ngs-unreportable was removed from gene: SLCO5A1.
Skeletal dysplasia v1.240 SULF1 Eleanor Williams Tag currently-ngs-unreportable was removed from gene: SULF1.
Skeletal dysplasia v1.240 SULF1 Eleanor Williams Classified gene: SULF1 as Green List (high evidence)
Skeletal dysplasia v1.240 SULF1 Eleanor Williams Added comment: Comment on list classification: Changing rating to green. Deletions covering this gene will be reported.
Skeletal dysplasia v1.240 SULF1 Eleanor Williams Gene: sulf1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.239 SLCO5A1 Eleanor Williams Classified gene: SLCO5A1 as Green List (high evidence)
Skeletal dysplasia v1.239 SLCO5A1 Eleanor Williams Added comment: Comment on list classification: Changing rating to green. Deletions covering this gene will be reported.
Skeletal dysplasia v1.239 SLCO5A1 Eleanor Williams Gene: slco5a1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.238 P4HB Eleanor Williams Mode of pathogenicity for gene: P4HB was changed from Other to Other
Skeletal dysplasia v1.237 P4HB Eleanor Williams Added comment: Comment on mode of pathogenicity: 1 missense variant reported to date + deletion of several exons.
Skeletal dysplasia v1.237 P4HB Eleanor Williams Mode of pathogenicity for gene: P4HB was changed from to Other
Skeletal dysplasia v1.236 P4HB Eleanor Williams Classified gene: P4HB as Green List (high evidence)
Skeletal dysplasia v1.236 P4HB Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. > 3 cases.
Including OI genes on this panel.
Skeletal dysplasia v1.236 P4HB Eleanor Williams Gene: p4hb has been classified as Green List (High Evidence).
Skeletal dysplasia v1.235 MASP1 Eleanor Williams Classified gene: MASP1 as Green List (high evidence)
Skeletal dysplasia v1.235 MASP1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. >3 cases reported. Skeletal phenotype.
Skeletal dysplasia v1.235 MASP1 Eleanor Williams Gene: masp1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.234 MASP1 Eleanor Williams Mode of inheritance for gene: MASP1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.233 MASP1 Eleanor Williams commented on gene: MASP1: Associated with 3MC syndrome 1 #257920 (AR) in OMIM. Post natal growth retardation and radioulnar synostosis as well as craniosynostosis are listed as clinical features.

6 families and 5 variants in MASP1 reported in OMIM.

COLEC11 associated with 3MC syndrome 2 is already green on the panel.
Skeletal dysplasia v1.233 MANBA Eleanor Williams Tag watchlist tag was added to gene: MANBA.
Skeletal dysplasia v1.233 MANBA Eleanor Williams Classified gene: MANBA as Amber List (moderate evidence)
Skeletal dysplasia v1.233 MANBA Eleanor Williams Added comment: Comment on list classification: Only 1 family reported with a strong skeletal phenotype so rating amber for now.
Skeletal dysplasia v1.233 MANBA Eleanor Williams Gene: manba has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.232 MANBA Eleanor Williams Publications for gene: MANBA were set to
Skeletal dysplasia v1.231 MANBA Eleanor Williams Mode of inheritance for gene: MANBA was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.230 MANBA Eleanor Williams commented on gene: MANBA: Associated with Mannosidosis, beta #248510 (AR) in OMIM. No clear skeletal phenotype listed in the clinical features in OMIM.

>3 cases reported with homozygous or compound het variants in OMIM.

PMID: 2079835 - Kleijer et al 1990 - report a family with Mannosidosis in which a homozygous variant in the MANBA gene was later identified by Alkhayat et al. (1998). Some affected individuals showed scoliosis, one individual showed deformities of the thorax, lumbar hyperlordosis and nanism.

PMID: 16401745 - Sedel et al 2006 - 1 case of boy with beta-mannosidase deficiency. No skeletal phenotype reported.
PMID: 18980795 - Labauge et al 2009 - 1 case of boy with beta-mannosidase deficiency. No skeletal phenotype reported.
Skeletal dysplasia v1.230 KMT2D Eleanor Williams Classified gene: KMT2D as Green List (high evidence)
Skeletal dysplasia v1.230 KMT2D Eleanor Williams Added comment: Comment on list classification: Promoting from red to green as >3 cases reported and phenotype is relevant.
Skeletal dysplasia v1.230 KMT2D Eleanor Williams Gene: kmt2d has been classified as Green List (High Evidence).
Skeletal dysplasia v1.229 KMT2D Eleanor Williams Mode of inheritance for gene: KMT2D was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v1.228 KMT2D Eleanor Williams commented on gene: KMT2D: Associated with Kabuki syndrome 1 #147920 (AD) in OMIM. Short stature and some skeletal features (spine, hips) listed as clinical features.

> 3 cases reported in OMIM.
Skeletal dysplasia v1.228 KMT2D Eleanor Williams commented on gene: KMT2D: Associated with Kabuki syndrome 1 #147920 (AD) in OMIM. Short stature and some skeletal features (spine, hips) listed as clinical features.

> 3 cases reported in OMIM.
Skeletal dysplasia v1.228 KAT6B Eleanor Williams Classified gene: KAT6B as Green List (high evidence)
Skeletal dysplasia v1.228 KAT6B Eleanor Williams Added comment: Comment on list classification: More than 3 cases reported.
Skeletal dysplasia v1.228 KAT6B Eleanor Williams Gene: kat6b has been classified as Green List (High Evidence).
Skeletal dysplasia v1.227 KAT6B Eleanor Williams Mode of inheritance for gene: KAT6B was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v1.226 KAT6B Eleanor Williams commented on gene: KAT6B: Associated with Genitopatellar syndrome #606170 (AD) in OMIM. Abnormalities of the pelvis, limbs, hands and feet listed. >3 cases reported in OMIM.
Skeletal dysplasia v1.226 KAT6A Eleanor Williams commented on gene: KAT6A: Associated with Mental retardation, autosomal dominant 32 #616268 (AD) in OMIM.

PMID: 25728777 -Tham et al 2015 - report six individuals from five unrelated families, with mutations in KAT6A detected by whole-exome sequencing. 5 different de novo heterozygous truncating mutations were identified. An additional subject with a 0.23 MB microdeletion including the entire KAT6A reading frame was identified with genome-wide array comparative genomic hybridization. Craniosynostosis was reported in 2 families. No other major skeletal abnormalities were reported.
Skeletal dysplasia v1.226 IGF1R Eleanor Williams commented on gene: IGF1R: Associated with Insulin-like growth factor I, resistance to #270450 (AD, AR). More than 3 cases with variants in IFG1R reported in OMIM. Clinical features include short stature due to lack of response to IGF. Clinodactyly and short hands and feet also listed.
Skeletal dysplasia v1.226 IFIH1 Eleanor Williams Classified gene: IFIH1 as Green List (high evidence)
Skeletal dysplasia v1.226 IFIH1 Eleanor Williams Added comment: Comment on list classification: 4 cases reported. All have the same gain of function variant. Genomics England clinicians confirm the phenotype is relevant.
Skeletal dysplasia v1.226 IFIH1 Eleanor Williams Gene: ifih1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.225 IFIH1 Eleanor Williams Phenotypes for gene: IFIH1 were changed from Singleton-Merten syndrome 1 (182250) to Singleton-Merten syndrome 1, 182250
Skeletal dysplasia v1.224 IFIH1 Eleanor Williams Publications for gene: IFIH1 were set to 25620204
Skeletal dysplasia v1.223 IFIH1 Eleanor Williams Added comment: Comment on mode of pathogenicity: A single variant, thought to act as a gain of function, has been identified.
Skeletal dysplasia v1.223 IFIH1 Eleanor Williams Mode of pathogenicity for gene: IFIH1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Skeletal dysplasia v1.222 IFIH1 Eleanor Williams Mode of inheritance for gene: IFIH1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v1.221 IFIH1 Eleanor Williams changed review comment from: Associated with Singleton-Merten syndrome 1 #182250 (AD) in OMIM with short stature and various skeletal abnormalities listed as clinical features.

PMID: 25620204 - Rutsch et al 2015 - identified the same missense mutation, c.2465G>A (p.Arg822Gln), in IFIH1 in Singleton-Merten syndrome (SMS) patients from two families and a simplex case. Functional studies suggest this is a a gain-of-function IFIH1 mutation. Patients showed early and extreme aortic and valvular calcification, dental anomalies, osteopenia, and acroosteolysis .; to: Associated with Singleton-Merten syndrome 1 #182250 (AD) in OMIM with short stature and various skeletal abnormalities listed as clinical features.

PMID: 25620204 - Rutsch et al 2015 - identified the same missense mutation, c.2465G>A (p.Arg822Gln), in IFIH1 in Singleton-Merten syndrome (SMS) patients from two families and a simplex case. Functional studies suggest this is a a gain-of-function IFIH1 mutation. Patients showed early and extreme aortic and valvular calcification, dental anomalies, osteopenia, and acroosteolysis .

PMID: 28319323 - Pettersson et al 2018 - identified the same mutation c.2465G>A p.(Arg822Gln), in IFIH1in a mother and daughter with Singleton-Merten syndrome. Patient 1 presented with congenital glaucoma, spastic paraplegia, severe dental anomalies, kyphosis, osteoporosis, recurrent infections, muscle weakness, aortic insufficiency, pericarditis, short stature, and SLE. Her mother presented with milder dental anomalies and finger deformities.
Skeletal dysplasia v1.221 IFIH1 Eleanor Williams commented on gene: IFIH1: Associated with Singleton-Merten syndrome 1 #182250 (AD) in OMIM with short stature and various skeletal abnormalities listed as clinical features.

PMID: 25620204 - Rutsch et al 2015 - identified the same missense mutation, c.2465G>A (p.Arg822Gln), in IFIH1 in Singleton-Merten syndrome (SMS) patients from two families and a simplex case. Functional studies suggest this is a a gain-of-function IFIH1 mutation. Patients showed early and extreme aortic and valvular calcification, dental anomalies, osteopenia, and acroosteolysis .
Skeletal dysplasia v1.221 IDH2 Eleanor Williams changed review comment from: Associated with D-2-hydroxyglutaric aciduria 2 #613657 in OMIM. No inheritance pattern given. Clinical features do not list skeletal characteristics.

PMID: 20847235 - Kranendijk et al. (2010) - 15 of 17 cases of D-2-hydroxyglutaric aciduria without mutation in the D2HGDH gene a heterozygous mutation was found in the IDH2 gene. 14 had an arg140-to-gln mutation (R140Q) and 1 had an arg140-to-gly mutation (R140G).

PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo.

PMID: 22057234 - Pansuriya etal 2011 - state that 'Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). They report somatic heterozygous mutations IDH2 (c.516G>C encoding R172S) in enchondromas (benign cartilage tumors) and in spindle cell hemangiomas (benign vascular lesions).

Conclusion - associated with D-2-hydroxyglutaric aciduria but this does not have a skeletal phenotype. Also associated with somatic mutations which can result in Ollier disease and Maffucci syndrome; to: Associated with D-2-hydroxyglutaric aciduria 2 #613657 in OMIM. No inheritance pattern given. Clinical features do not list skeletal characteristics.

PMID: 20847235 - Kranendijk et al. (2010) - 15 of 17 cases of D-2-hydroxyglutaric aciduria without mutation in the D2HGDH gene a heterozygous mutation was found in the IDH2 gene. 14 had an arg140-to-gln mutation (R140Q) and 1 had an arg140-to-gly mutation (R140G). Phenotypes of the patients are not given.

PMID: 24049096 - Nota et al. (2013) reported two patients with D-2-hydroxyglutaric aciduria-2, one in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo. In the other the mother also had mosacism for R140Q variant. No skeletal phenotypes are reported.

PMID: 22057234 - Pansuriya etal 2011 - state that 'Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). They report somatic heterozygous mutations IDH2 (c.516G>C encoding R172S) in enchondromas (benign cartilage tumors) and in spindle cell hemangiomas (benign vascular lesions).

Conclusion - associated with D-2-hydroxyglutaric aciduria but this does not have a skeletal phenotype. Also associated with somatic mutations which can result in Ollier disease and Maffucci syndrome
Skeletal dysplasia v1.221 IDH2 Eleanor Williams changed review comment from: PMID: 20847235 - Kranendijk et al. (2010) - 15 of 17 cases of D-2-hydroxyglutaric aciduria without mutation in the D2HGDH gene a heterozygous mutation was found in the IDH2 gene. 14 had an arg140-to-gln mutation (R140Q) and 1 had an arg140-to-gly mutation (R140G).

PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo.; to: Associated with D-2-hydroxyglutaric aciduria 2 #613657 in OMIM. No inheritance pattern given. Clinical features do not list skeletal characteristics.

PMID: 20847235 - Kranendijk et al. (2010) - 15 of 17 cases of D-2-hydroxyglutaric aciduria without mutation in the D2HGDH gene a heterozygous mutation was found in the IDH2 gene. 14 had an arg140-to-gln mutation (R140Q) and 1 had an arg140-to-gly mutation (R140G).

PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo.

PMID: 22057234 - Pansuriya etal 2011 - state that 'Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). They report somatic heterozygous mutations IDH2 (c.516G>C encoding R172S) in enchondromas (benign cartilage tumors) and in spindle cell hemangiomas (benign vascular lesions).

Conclusion - associated with D-2-hydroxyglutaric aciduria but this does not have a skeletal phenotype. Also associated with somatic mutations which can result in Ollier disease and Maffucci syndrome
Skeletal dysplasia v1.221 EP300 Eleanor Williams commented on gene: EP300: Associated with Rubinstein-Taybi syndrome 2 #613684 (AD) in OMIM with Broad thumbs, Square distal fingertips, Syndactyly (in some patients) and Broad great toes listed as skeletal clinical features.

Heterozygous mutations reported in > 3 cases in OMIM.
Skeletal dysplasia v1.221 COG1 Eleanor Williams Classified gene: COG1 as Green List (high evidence)
Skeletal dysplasia v1.221 COG1 Eleanor Williams Added comment: Comment on list classification: 3 unrelated cases with plausible disease causing variants in the gene reported and a relevant phenotype.
Skeletal dysplasia v1.221 COG1 Eleanor Williams Gene: cog1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.220 COG1 Eleanor Williams changed review comment from: Associated with Congenital disorder of glycosylation, type IIg #611209 (AR) in OMIM.; to: Associated with Congenital disorder of glycosylation, type IIg #611209 (AR) in OMIM. Clinical features include short stature, several skeletal features such as scoliosis and vertebral abnormalities.

PMID: 16537452 - Foulquier et al 2006 - describe a patient with a mild form of congenital disorder of glycosylation type II with a homozygous insertion of a single nucleotide (2659-2660insC), which is predicted to lead to a premature translation stop and truncation of the C terminus of the Cog1 protein by 80 amino acids. Both parents were shown to be heterozygous for this mutation. Her skeletal features included small hands and feet, rhizomelic short stature.

PMID: 19008299 - Zeevaert et al 2009 - two patients (one with consanguineous Greek-Turkish parents, the other with unrelated Bulgarian parents) with a cerebrocostomandibular-like syndrome and an intronic mutation, c.1070+5G>A, that disrupts a splice donor site and leads to skipping of exon 6, a frameshift and a premature stopcodon in exon 7. Patient 1's characteristics included multiple congenital abnormalities including Pierre-Robin sequence (cleft palate, micrognathia and glossoptosis), costovertebral anomalies including osteopenia, ribfusions and posterior rib gaps, butterfly vertebrae, misalignment of the vertebrae and a clubfoot on the right. Patient 2 presented with rhizomelic shortening of upper limbs, ulnar deviation of fingers, thoracic scoliosis, hypospadias-I and left-side cryptorchidism among other features.

3 unrelated cases.
Skeletal dysplasia v1.220 COG1 Eleanor Williams commented on gene: COG1: Associated with Congenital disorder of glycosylation, type IIg #611209 (AR) in OMIM.
Skeletal dysplasia v1.220 SULF1 Eleanor Williams Tag deletions tag was added to gene: SULF1.
Tag currently-ngs-unreportable tag was added to gene: SULF1.
Skeletal dysplasia v1.220 SLCO5A1 Eleanor Williams Tag deletions tag was added to gene: SLCO5A1.
Tag currently-ngs-unreportable tag was added to gene: SLCO5A1.
Skeletal dysplasia v1.220 OAT Eleanor Williams changed review comment from: Associated with Gyrate atrophy of choroid and retina with or without ornithinemia #258870 (AR) in OMIM but no skeletal phenotypes listed in clinical features.

This gene is not listed in Bonafe et al 2015 (Nosology and Classification of Genetic Skeletal Disorders: 2015 Revision) PMID: 26394607 or Mortier et al 2019 (Nosology and classification of genetic skeletal disorders: 2019 revision). PMID: 31633310; to: Associated with Gyrate atrophy of choroid and retina with or without ornithinemia #258870 (AR) in OMIM but no skeletal phenotypes listed in clinical features.

This gene is not listed in Bonafe et al 2015 (Nosology and Classification of Genetic Skeletal Disorders: 2015 Revision) PMID: 26394607 or Mortier et al 2019 (Nosology and classification of genetic skeletal disorders: 2019 revision). PMID: 31633310

A PubMed search did not find any relevant publications.
Skeletal dysplasia v1.220 SULF1 Eleanor Williams commented on gene: SULF1: Not associated with any phenotype in OMIM or Gene2Phenotype.

PMID: 20602915 - Isidor et al 2010 - using whole-genome oligonucleotide array CGH, they identified an interstitial deletion at 8q13 in 5 patients from 4 unrelated families with Mesomelia-synostoses syndrome. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1 and SLCO5A1. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Codeletion of SULF1 and SLCO5A1was found in all patients, suggesting that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS.

PMID: 28328141 - Kohmoto et al 2017 - report the first Japanese case with MSS diagnosed by detecting an 8q13 deletion (581 Kb monoallelic deletion) that resulted from a unique, distant L1s‐mediated unequal NAHR event, which is different from the possible mechanisms proposed in previously reported cases. The deletion encompasses SULF1, SLCO5A1, and LINC01603. The size of the 8q13 deletion was different from those of any of the four reported deletions responsible for MSS (Isidor et al., 2010). The deletion could not be confirmed as de novo because of the unavailability of parental DNA.

PMID: 30450550 - Dardis et al 2019 - describe the first patient affected by MSS without the previously described 8q13 deletions. Patient is an 8‐year‐old 46,XY male presenting the radiological and clinical hallmarks of MSS. Microdeletions of SULF1 and SLCO5A1 genes at 8q13 were absent. Sequencing of SULF1 and SLCO5A1 found 4 polymorphisms but no pathogenic mutations. However, it was found that there was monoallelic expression of SULF1 in the patient's cells, likely leading to SULF1 haploinsufficiency. There may be either a deletion of a portion of SULF1 gene not detectable by PCR or CGH array or mutations or epigenetic alterations in sequences that contribute to the regulation of SULF1 expression.

Summary, there are 5 cases where deletions covering both SULF1 and SLCO5A1 are found in patients with MSS. There is one case of MSS in a patient with no detectable deletions of SULF1 and SLCO5A1, but with monoallelic expression of SULF1. There is no current regions curated by ClinGen that cover these genes.
Skeletal dysplasia v1.220 SLCO5A1 Eleanor Williams commented on gene: SLCO5A1: Not associated with any phenotype in OMIM or Gene2Phenotype.

PMID: 20602915 - Isidor et al 2010 - using whole-genome oligonucleotide array CGH, they identified an interstitial deletion at 8q13 in 5 patients from 4 unrelated families with Mesomelia-synostoses syndrome. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1 and SLCO5A1. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Codeletion of SULF1 and SLCO5A1was found in all patients, suggesting that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS.

PMID: 28328141 - Kohmoto et al 2017 - report the first Japanese case with MSS diagnosed by detecting an 8q13 deletion (581 Kb monoallelic deletion) that resulted from a unique, distant L1s‐mediated unequal NAHR event, which is different from the possible mechanisms proposed in previously reported cases. The deletion encompasses SULF1, SLCO5A1, and LINC01603. The size of the 8q13 deletion was different from those of any of the four reported deletions responsible for MSS (Isidor et al., 2010). The deletion could not be confirmed as de novo because of the unavailability of parental DNA.

PMID: 30450550 - Dardis et al 2019 - describe the first patient affected by MSS without the previously described 8q13 deletions. Patient is an 8‐year‐old 46,XY male presenting the radiological and clinical hallmarks of MSS. Microdeletions of SULF1 and SLCO5A1 genes at 8q13 were absent. Sequencing of SULF1 and SLCO5A1 found 4 polymorphisms but no pathogenic mutations. However, it was found that there was monoallelic expression of SULF1 in the patient's cells, likely leading to SULF1 haploinsufficiency. There may be either a deletion of a portion of SULF1 gene not detectable by PCR or CGH array or mutations or epigenetic alterations in sequences that contribute to the regulation of SULF1 expression.

Summary, there are 5 cases where deletions covering both SULF1 and SLCO5A1 are found in patients with MSS. There is one case of MSS in a patient with no detectable deletions of SULF1 and SLCO5A1, but with monoallelic expression of SULF1. There is no current regions curated by ClinGen that cover these genes.
Skeletal dysplasia v1.220 RAD21 Eleanor Williams changed review comment from: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects.

OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified.

Other publications with patients with Cornelia de Lange and RAD21 variants
PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay.
PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance.
PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance
PMID: 27620904 - Martinez et al., 2017 - 1 patient; to: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects.

OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified.

Other publications with patients with Cornelia de Lange and RAD21 variants:

PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay.

PMID: 24378232 - Minor et al., 2014 - 2 patients with atypic Cornelia de Lange. Patient 1 - in frame deletion of exon 13 - presented with developmental delay, hypospadias, inguinal hernia and dysmorphic features, mild 5th finger clinodactyly. This deletion was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems.
Patient 2 - c.592_593dup frameshift mutation - presented with developmental delay, characteristic facial features, hirsutism, and hand and feet anomalies (clinodactyly, syndactyly). The mother had the same frameshift mutation showing incomplete penetrance.

PMID: 27882533 - Boyle et al., 2017 - patient with microcephaly and classical CdLS facial features with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance.

PMID: 27620904 - Martinez et al., 2017 - 92 patients recruited with syndromic intellectual disability. 1 patient identified with a variant in RAD21. A diagnosis of CdLS was made.
Skeletal dysplasia v1.220 RAD21 Eleanor Williams Classified gene: RAD21 as Amber List (moderate evidence)
Skeletal dysplasia v1.220 RAD21 Eleanor Williams Added comment: Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects (2 cases). Other cases of deletions covering this gene and a similar phenotype are also reported.
Skeletal dysplasia v1.220 RAD21 Eleanor Williams Gene: rad21 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.219 RAD21 Eleanor Williams changed review comment from: Associated with Cornelia de Lange syndrome 4 614701 in OMIM.

OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified.

Other publications with patients with Cornelia de Lange and RAD21 variants
PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay.
PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance.
PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance
PMID: 27620904 - Martinez et al., 2017 - 1 patient; to: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects.

OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified.

Other publications with patients with Cornelia de Lange and RAD21 variants
PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay.
PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance.
PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance
PMID: 27620904 - Martinez et al., 2017 - 1 patient
Skeletal dysplasia v1.219 RAD21 Eleanor Williams changed review comment from: Associated with Cornelia de Lange syndrome 4 614701 in OMIM.

OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short and thin fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified.

Other publications with patients with Cornelia de Lange and RAD21 variants
PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay.
PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance.
PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance
PMID: 27620904 - Martinez et al., 2017 - 1 patient; to: Associated with Cornelia de Lange syndrome 4 614701 in OMIM.

OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified.

Other publications with patients with Cornelia de Lange and RAD21 variants
PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay.
PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance.
PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance
PMID: 27620904 - Martinez et al., 2017 - 1 patient
Skeletal dysplasia v1.219 RAD21 Eleanor Williams changed review comment from: OMIM: - 2 cases reported in OMIM (PMID: 22633399, Deardorff et al 2012) plus 3 patients with overlapping deletions covering RAD21 (aswell as other genes).

Other publications with patients with Cornelia de Lange and RAD21 variants
PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype
PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance.
PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance
PMID: 27620904 - Martinez et al., 2017 - 1 patient; to: Associated with Cornelia de Lange syndrome 4 614701 in OMIM.

OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short and thin fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified.

Other publications with patients with Cornelia de Lange and RAD21 variants
PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay.
PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance.
PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance
PMID: 27620904 - Martinez et al., 2017 - 1 patient
Skeletal dysplasia v1.219 OAT Eleanor Williams commented on gene: OAT: Associated with Gyrate atrophy of choroid and retina with or without ornithinemia #258870 (AR) in OMIM but no skeletal phenotypes listed in clinical features.

This gene is not listed in Bonafe et al 2015 (Nosology and Classification of Genetic Skeletal Disorders: 2015 Revision) PMID: 26394607 or Mortier et al 2019 (Nosology and classification of genetic skeletal disorders: 2019 revision). PMID: 31633310
Skeletal dysplasia v1.219 CKAP2L Eleanor Williams commented on gene: CKAP2L: Associated with Filippi syndrome #272440 (AR) in OMIM. Mainly a digital phenotype.

PMID: 25439729 - Hussain et al 2014 - performed homozygosity mapping and whole-exome sequencing in a Sardinian family with two children with Filippi syndrome and identified a homozygous frameshift mutation, c.571dupA (p.Ile191Asnfs∗6), in CKAP2L which segregated with the disease in the family. They then sequenced CKAP2L in eight additional Filippi-syndrome-affected families (one from Italy, one from Poland, one from Turkey, and five from the UK) and identified five additional mutations in four of the further eight families affected by Filippi syndrome.

Sufficient cases reported, but need to assess whether the phenotype is appropriate for the skeletal dysplasia panel. It is green on the Limb disorders panel.
Skeletal dysplasia v1.219 ARID1B Eleanor Williams commented on gene: ARID1B: Associated with Coffin-Siris syndrome 1 #135900 (AD) in OMIM. Clinical features list short stature in some patients, but mainly a limb phenotype including hypoplastic digits and nails.

OMIM lists many cases of variants in ARID1B reported in patients with Coffin-Siris syndrome.
Skeletal dysplasia v1.219 AKT1 Eleanor Williams changed review comment from: Associated with several phenotypes in OMIM including Proteus syndrome, somatic # 176920. Proteus syndrome features overgrowth of body parts and is associated with mosaicism for a somatic activating mutation in the AKT1 gene.

The Genomics England clinical team do not consider this appropriate for a green rating on the skeletal dysplasia panel.; to: Associated with several phenotypes in OMIM including Proteus syndrome, somatic # 176920. Proteus syndrome features overgrowth of body parts and is associated with mosaicism for a somatic activating mutation in the AKT1 gene.

PMID: 21793738 - Lindhurst et al 2011 - Of 29 patients with the Proteus syndrome, 26 had a somatic activating mutation (c.49G→A, p.Glu17Lys) in the oncogene AKT1. Tissues and cell lines from patients with the Proteus syndrome harbored admixtures of mutant alleles that ranged from 1% to approximately 50%. Mutant cell lines showed greater AKT phosphorylation than did control cell lines.

The Genomics England clinical team do not consider this appropriate for a green rating on the skeletal dysplasia panel.
Skeletal dysplasia v1.219 AKT1 Eleanor Williams commented on gene: AKT1: Associated with several phenotypes in OMIM including Proteus syndrome, somatic # 176920. Proteus syndrome features overgrowth of body parts and is associated with mosaicism for a somatic activating mutation in the AKT1 gene.

The Genomics England clinical team do not consider this appropriate for a green rating on the skeletal dysplasia panel.
Skeletal dysplasia v1.219 TWIST2 Eleanor Williams Classified gene: TWIST2 as No list
Skeletal dysplasia v1.219 TWIST2 Eleanor Williams Added comment: Comment on list classification: Removing this gene from the panel as the OMIM phenotypes to not have a clear skeletal phenotype.
Skeletal dysplasia v1.219 TWIST2 Eleanor Williams Gene: twist2 has been removed from the panel.
Skeletal dysplasia v1.218 THPO Eleanor Williams Classified gene: THPO as Red List (low evidence)
Skeletal dysplasia v1.218 THPO Eleanor Williams Added comment: Comment on list classification: Demoted from Green to red. Only two cases reported with a limb defect and no clear wider skeletal phenotype.
Skeletal dysplasia v1.218 THPO Eleanor Williams Gene: thpo has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.217 THPO Eleanor Williams commented on gene: THPO: Associated with Thrombocythemia 1 #187950 (AD) in OMIM.


PMID: 19553636 - Graziano et al 2009 - report where the father has thrombocythemia and limb defects (absence of forearm and hand, absence of foot). Two sons had milder lower limb defects. A G185T heterozygous mutation was detected in THPO. The grandfather was found to have the variant and had thrombocythemia but no limb defect.

PMID: 22453305 - Stockklausner et al 2012 - report two families with Hereditary thrombocythemia resulting from a THPO c.13+1 G>C mutation in the splice donor of intron 3. In one family there were coexisting distal limb defects in 2 out of 4 individuals with thrombocythemia (complex limb defects of the left hand in one individual, and absent proximal, middle, and distal phalanges at digits 3–5, a dysplastic proximal phalanx at digit 2 with absent middle and distal phalanx and shortened metacarpal bones at digits 3 and 4, carpal bones were partly fused to metacarpal bones at digits 2–5 in the other).
Skeletal dysplasia v1.217 ASXL1 Eleanor Williams changed review comment from: Associated with Bohring-Opitz syndrome #605039 (AD) in OMIM. Clinical features listed include short stature and a number of skeletal features including upper limb rhizomelia.; to: Associated with Bohring-Opitz syndrome #605039 (AD) in OMIM. Clinical features listed include short stature and a number of skeletal features including upper limb rhizomelia.

Genomics England clinical team feel that there are sufficient relevant phenotypes to leave green.
Skeletal dysplasia v1.217 ASXL1 Eleanor Williams commented on gene: ASXL1: Associated with Bohring-Opitz syndrome #605039 (AD) in OMIM. Clinical features listed include short stature and a number of skeletal features including upper limb rhizomelia.
Skeletal dysplasia v1.217 TGDS Eleanor Williams commented on gene: TGDS: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM.

PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation


In 7 patients with Catel-Manzke syndrome (616145), Ehmke et al. (2014) identified homozygosity or compound heterozygosity for mutations in the TGDS gene
Skeletal dysplasia v1.217 WRN Eleanor Williams Mode of inheritance for gene: WRN was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.217 WRN Eleanor Williams Mode of inheritance for gene: WRN was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.216 WRN Eleanor Williams commented on gene: WRN: Associated with Werner syndrome #277700 (AR) in OMIM with Osteoporosis and slender limbs listed as clinical features.
From Genetics Home Reference "Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. Individuals with this disorder typically grow and develop normally until they reach puberty. Affected teenagers usually do not have a growth spurt, resulting in short stature".

Numerous variants reported in the RECQL2/WRN gene in association with Werner syndrome in OMIM.
Skeletal dysplasia v1.216 PIK3C2A Eleanor Williams Classified gene: PIK3C2A as Green List (high evidence)
Skeletal dysplasia v1.216 PIK3C2A Eleanor Williams Added comment: Comment on list classification: After further assessment of the phenotype in the supplementary data for PMID: 31034465 (scoliosis, short stature etc) it was decided to promote this gene to green
Skeletal dysplasia v1.216 PIK3C2A Eleanor Williams Gene: pik3c2a has been classified as Green List (High Evidence).
Skeletal dysplasia v1.215 TMEM67 Eleanor Williams Classified gene: TMEM67 as Red List (low evidence)
Skeletal dysplasia v1.215 TMEM67 Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team demoting this gene to red as the skeletal phenotype is not strong.
Skeletal dysplasia v1.215 TMEM67 Eleanor Williams Gene: tmem67 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.214 KIAA0753 Eleanor Williams Classified gene: KIAA0753 as Green List (high evidence)
Skeletal dysplasia v1.214 KIAA0753 Eleanor Williams Added comment: Comment on list classification: Adding this ciliopathy gene to the skeletal dysplasia panel after consultation with the Genomics England clinical team. The reported phenotypes include skeletal dysplasias.
Skeletal dysplasia v1.214 KIAA0753 Eleanor Williams Gene: kiaa0753 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.213 KIAA0753 Eleanor Williams gene: KIAA0753 was added
gene: KIAA0753 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: KIAA0753 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0753 were set to 29138412; 28220259; 26643951
Phenotypes for gene: KIAA0753 were set to ?Orofaciodigital syndrome XV 617127; Joubert syndrome; Short-rib skeletal dysplasia
Review for gene: KIAA0753 was set to GREEN
Added comment: Provisionally associated with ?Orofaciodigital syndrome XV (617127) in OMIM

PMID: 26643951 - Chevrier et al 2016 - 1 case of a newborn female presenting with an oral-facial-digital (OFD) VI syndrome in which they identified two causal heterozygous mutations in the KIAA0753 gene. Both KIAA0753 mutations, one nonsense variant (c.1891A>T; p.Lys631*) and one substitution in Intron 8 (c.1546-3C>A), were confirmed by Sanger sequencing, as well as the maternal heterozygous status for the non-sense variant.

PMID: 28220259 - Stephen et al 2017 - 2 siblings with Joubert syndrome associated with growth hormone deficiency but no oral or digital anomalies. Whole exome sequencing of the family identified compound heterozygous mutations in KIAA0753, i.e., a missense mutation (p.Arg257Gly) and an intronic mutation (c.2359-1G>C).

PMID: 29138412 - Hammarsjö et al 2017 - report biallelic pathogenic variants in KIAA0753 in four patients from 3 families with short-rib type skeletal dysplasia - ranging from prenatal lethality in one fetus to viability with moderate skeletal dysplasia in three children. 2 families had the same homozygous nonsense variant but are not thought to be related. In the 3rd family the index patient was compound heterogyzous. KIAA0753 is expressed in normal fetal human growth plate and they show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning. In family 1, they also identified an additional homozygous missense variant, c.425 C > T (p.Thr142Met) in SLC13A5 and conclude that the seizures and teeth hypoplasia in P1 and P2 are due to the homozygous SLC13A5 variant.
Sources: Other
Skeletal dysplasia v1.212 ZSWIM6 Eleanor Williams Classified gene: ZSWIM6 as Green List (high evidence)
Skeletal dysplasia v1.212 ZSWIM6 Eleanor Williams Added comment: Comment on list classification: This cililiopathy gene has been added to the skeletal dysplasia panel after consultation with the Genomics England clinical team. There is sufficient skeletal involvement to include on this panel.
Skeletal dysplasia v1.212 ZSWIM6 Eleanor Williams Gene: zswim6 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.211 ZSWIM6 Eleanor Williams gene: ZSWIM6 was added
gene: ZSWIM6 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZSWIM6 were set to 25105228
Phenotypes for gene: ZSWIM6 were set to Acromelic frontonasal dysostosis 603671
Review for gene: ZSWIM6 was set to GREEN
Added comment: Associated with Acromelic frontonasal dysostosis #603671 (AD) and Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features #617865 (AD) in OMIM. Acromelic frontonasal dysostosis - OMIM lists the skeletal phenotypes of Patellar hypoplasia or aplasia (in some patients), Tibial hypoplasia, polydactyly of hands and feet, Talipes equinovarus. Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features - OMIM lists the skeletal phenotype of Foot deformities (in some patients) only
Sources: Other
Skeletal dysplasia v1.210 DHCR7 Eleanor Williams Classified gene: DHCR7 as Green List (high evidence)
Skeletal dysplasia v1.210 DHCR7 Eleanor Williams Added comment: Comment on list classification: This ciliopathy gene is being added to the Skeletal dysplasia panel after discussion with the Genomics England clinical team. Smith-Lemli-Optiz syndrome includes features such as limb shortening as well as abnormalities of the hands and feet.
Skeletal dysplasia v1.210 DHCR7 Eleanor Williams Gene: dhcr7 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.209 DHCR7 Eleanor Williams gene: DHCR7 was added
gene: DHCR7 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to 9634533
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome 270400
Review for gene: DHCR7 was set to GREEN
Added comment: Associated with Smith-Lemli-Opitz syndrome in OMIM. They describe this as "an autosomal recessive multiple congenital malformation and mental retardation syndrome." Several skeletal features are listed in the clinical features in OMIM including limb shortening, Hip dislocation and subluxation, and abnormalities of the hands and feet.
Sources: Other
Skeletal dysplasia v1.208 PIK3C2A Eleanor Williams Phenotypes for gene: PIK3C2A were changed from to Oculoskeletodental syndrome 618440
Skeletal dysplasia v1.207 PIK3C2A Eleanor Williams Classified gene: PIK3C2A as Amber List (moderate evidence)
Skeletal dysplasia v1.207 PIK3C2A Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team, decided to rate this gene Amber for now. Not clear how relevant the skeletal phenotypes are to this panel.
Skeletal dysplasia v1.207 PIK3C2A Eleanor Williams Gene: pik3c2a has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.206 PIK3C2A Eleanor Williams gene: PIK3C2A was added
gene: PIK3C2A was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3C2A were set to 31034465
Review for gene: PIK3C2A was set to AMBER
Added comment: Associated with Oculoskeletodental syndrome #618440 (AR) in OMIM. This is based on evidence from PMID: 31034465 - Tiosano et al 2019 - report 5 individuals from 3 unrelated consanguineous families with a similar set of clinical features including dysmorphic facial features, short stature, skeletal and neurological abnormalities, and cataracts. The skeletal findings included "scoliosis, delayed bone age, diminished ossification of femoral heads, cervical lordosis, shortened fifth digits with mild metaphyseal dysplasia and clinodactyly". Homozygous loss-of-function mutations in PIK3C2A were identified in each family.
Sources: Literature
Skeletal dysplasia v1.205 RPL13 Eleanor Williams changed review comment from: PMID: 31630789 - Le Caignec et al 2019 - report one de novo missense variant (c.548G>C [p.Arg183Pro]) and three de novo splice variants in RPL13, which encodes ribosomal protein RPL13, in four unrelated individuals with a rare bone dysplasia causing severe short stature. The three splice variants (c.477þ1G>T, c.477þ1G>A, and c.477þ2 T>C) result in partial intron retention, which leads to an 18-amino acid insertion.
Sources: Literature; to: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 31630789 - Le Caignec et al 2019 - report one de novo missense variant (c.548G>C [p.Arg183Pro]) and three de novo splice variants in RPL13, which encodes ribosomal protein RPL13, in four unrelated individuals with a rare bone dysplasia causing severe short stature. The three splice variants (c.477þ1G>T, c.477þ1G>A, and c.477þ2 T>C) result in partial intron retention, which leads to an 18-amino acid insertion.
Sources: Literature
Skeletal dysplasia v1.205 RPL13 Eleanor Williams Classified gene: RPL13 as Green List (high evidence)
Skeletal dysplasia v1.205 RPL13 Eleanor Williams Added comment: Comment on list classification: Promoting this gene to green as 4 cases, one with a missense variant but 3 with splice variants that lead to an 18 amino acid insertion in the protein have been reported.
Skeletal dysplasia v1.205 RPL13 Eleanor Williams Gene: rpl13 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.204 TMEM67 Eleanor Williams changed review comment from: Associated with several phenotypes in OMIM but ?RHYNS syndrome (#609884) is the main disease phenotype that has a skeletal component. Polydactyly may also be seen in Meckel syndrome 3 (#607361).

RHYNS syndrome - 1 case:

PMID: 9375913 - Di Rocco et al. (1997) - 1 case. 17.5-year-old boy with short stature, severe bone-age retardation and exhibited mild signs of skeletal dysplasia, including generalized osteopenia, epiphyseal hypoplasia, hypoplastic iliac bones with irregular acetabular margins, and thin tubular bones. He later developed nephronophthisis. Brancati et al. (2018) (PMID: 29891882) re-assessed this patient at age 38 years and reported he exhibited short stature and severe generalized osteoporosis. Skeletal survey showed moderately shortened long bones, bowed radii, short femoral neck, brachydactyly of the hands and feet with more severe involvement of middle phalanges, distal phalanx of the thumbs, and metacarpals, moderately thickened calvarium, and rotoscoliosis. Compound heterozygous variants in TMEM67 were identified, one inherited from each of his parents.

PMID: 11391657 - Hedera and Gorski (2001) described 2 brothers, who had early onset retinitis pigmentosa, short stature with GH deficiency, mild facial asymmetry, and acromelic shortening of the distal extremities. They suggest this phenotype is consistent with RHYNS syndrome but no genome analysis was done.

Meckel syndrome 3 - 3 out of 22 cases show polydactyly:

PMID: 16415887 - Smith et al. 2006 - detected 5 different homozygous mutations in the TMEM67 in 5 consanguineous families with Meckel syndrome. The mutations were not found in over 120 ethnically matched normal control chromosomes. Polydactyly was observed in 2 out of the 5 families.

PMID: 17377820 - Consugar et al. 2007 - identified 7 novel pathogenic mutations in the TMEM67 gene in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All cases were compound heterogygous. Polydactyly is reported in 1 family.; to: Associated with several phenotypes in OMIM but ?RHYNS syndrome (#609884) is the main disease phenotype that has a skeletal component. Polydactyly may also be seen in Meckel syndrome 3 (#607361).

RHYNS syndrome - 1 case:

PMID: 9375913 - Di Rocco et al. (1997) - 1 case. 17.5-year-old boy with short stature, severe bone-age retardation and exhibited mild signs of skeletal dysplasia, including generalized osteopenia, epiphyseal hypoplasia, hypoplastic iliac bones with irregular acetabular margins, and thin tubular bones. He later developed nephronophthisis. Brancati et al. (2018) (PMID: 29891882) re-assessed this patient at age 38 years and reported he exhibited short stature and severe generalized osteoporosis. Skeletal survey showed moderately shortened long bones, bowed radii, short femoral neck, brachydactyly of the hands and feet with more severe involvement of middle phalanges, distal phalanx of the thumbs, and metacarpals, moderately thickened calvarium, and rotoscoliosis. Compound heterozygous variants in TMEM67 were identified, one inherited from each of his parents.

PMID: 11391657 - Hedera and Gorski (2001) described 2 brothers, who had early onset retinitis pigmentosa, short stature with GH deficiency, mild facial asymmetry, and acromelic shortening of the distal extremities. They suggest this phenotype is consistent with RHYNS syndrome but no genome analysis was done.

Meckel syndrome 3 - 3 out of 22 cases show polydactyly:

PMID: 16415887 - Smith et al. 2006 - detected 5 different homozygous mutations in the TMEM67 in 5 consanguineous families with Meckel syndrome. The mutations were not found in over 120 ethnically matched normal control chromosomes. Polydactyly was observed in 2 out of the 5 families.

PMID: 17377820 - Consugar et al. 2007 - identified 7 novel pathogenic mutations in the TMEM67 gene in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All cases were compound heterogygous. Polydactyly is reported in 1 family.
Skeletal dysplasia v1.204 RPL13 Eleanor Williams gene: RPL13 was added
gene: RPL13 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: RPL13 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL13 were set to 31630789
Phenotypes for gene: RPL13 were set to Spondyloepimetaphyseal Dysplasia with Severe Short Stature
Review for gene: RPL13 was set to GREEN
Added comment: PMID: 31630789 - Le Caignec et al 2019 - report one de novo missense variant (c.548G>C [p.Arg183Pro]) and three de novo splice variants in RPL13, which encodes ribosomal protein RPL13, in four unrelated individuals with a rare bone dysplasia causing severe short stature. The three splice variants (c.477þ1G>T, c.477þ1G>A, and c.477þ2 T>C) result in partial intron retention, which leads to an 18-amino acid insertion.
Sources: Literature
Skeletal dysplasia v1.203 HDAC4 Eleanor Williams changed review comment from: Comment on list classification: After review with members of the GMS Musculoskeletal specialist test group and Genomics England Clinicians it was decided to rate the HDAC4 gene amber for SNVs, but to keep the region
ISCA-37394-Loss (2q37.3 terminal region (includes HDAC4) Loss) green.; to: Comment on list classification: After review with members of the GMS Musculoskeletal specialist test group and Genomics England Clinicians it was decided to rate the HDAC4 gene amber for SNVs, but to keep the region covering this gene green (ISCA-37394-Loss (2q37.3 terminal region (includes HDAC4) Loss))
Skeletal dysplasia v1.203 HDAC4 Eleanor Williams Classified gene: HDAC4 as Amber List (moderate evidence)
Skeletal dysplasia v1.203 HDAC4 Eleanor Williams Added comment: Comment on list classification: After review with members of the GMS Musculoskeletal specialist test group and Genomics England Clinicians it was decided to rate the HDAC4 gene amber for SNVs, but to keep the region
ISCA-37394-Loss (2q37.3 terminal region (includes HDAC4) Loss) green.
Skeletal dysplasia v1.203 HDAC4 Eleanor Williams Gene: hdac4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.202 ICK Eleanor Williams commented on gene: ICK: Added new-gene-name tag, new approved HGNC gene symbol for ICK is CILK1
Skeletal dysplasia v1.202 ICK Eleanor Williams Tag new-gene-name tag was added to gene: ICK.
Skeletal dysplasia v1.202 GZF1 Eleanor Williams Classified gene: GZF1 as Amber List (moderate evidence)
Skeletal dysplasia v1.202 GZF1 Eleanor Williams Added comment: Comment on list classification: Demoting from green to amber. 2 cases plus functional data, but the functional data does not strongly support a skeletal phenotype.
Skeletal dysplasia v1.202 GZF1 Eleanor Williams Gene: gzf1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.201 NIN Eleanor Williams Classified gene: NIN as Red List (low evidence)
Skeletal dysplasia v1.201 NIN Eleanor Williams Added comment: Comment on list classification: Changing rating from green to red, in light of Zornitza Stark's red review. Evidence is not strong.
Skeletal dysplasia v1.201 NIN Eleanor Williams Gene: nin has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.200 CREB3L1 Eleanor Williams changed review comment from: Comment on list classification: Decided to wait for GMS approval before upgrading to green.; to: Comment on list classification: Decided to wait for GMS approval before upgrading to green. Demoting back to red.
Skeletal dysplasia v1.200 DSPP Eleanor Williams Classified gene: DSPP as Red List (low evidence)
Skeletal dysplasia v1.200 DSPP Eleanor Williams Added comment: Comment on list classification: Decided to wait for GMS approval before upgrading to green on this panel. Demoting back to red.
Skeletal dysplasia v1.200 DSPP Eleanor Williams Gene: dspp has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.199 CREB3L1 Eleanor Williams Classified gene: CREB3L1 as Red List (low evidence)
Skeletal dysplasia v1.199 CREB3L1 Eleanor Williams Added comment: Comment on list classification: Decided to wait for GMS approval before upgrading to green.
Skeletal dysplasia v1.199 CREB3L1 Eleanor Williams Gene: creb3l1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.198 CREB3L1 Eleanor Williams changed review comment from: Comment on list classification: Upgrading from red to green. Is Green on the Osteogenesis imperfecta panel and 4 cases reported.; to: Comment on list classification: Upgrading from red to green. Is Green on the Osteogenesis imperfecta panel and 4 cases reported.
Skeletal dysplasia v1.198 DSPP Eleanor Williams Classified gene: DSPP as Green List (high evidence)
Skeletal dysplasia v1.198 DSPP Eleanor Williams Added comment: Comment on list classification: Green on the Osteogenesis imperfecta panel so making green on this panel.
Skeletal dysplasia v1.198 DSPP Eleanor Williams Gene: dspp has been classified as Green List (High Evidence).
Skeletal dysplasia v1.197 DSPP Eleanor Williams Publications for gene: DSPP were set to
Skeletal dysplasia v1.196 DSPP Eleanor Williams Mode of inheritance for gene: DSPP was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.195 DSPP Eleanor Williams commented on gene: DSPP
Skeletal dysplasia v1.195 CREB3L1 Eleanor Williams Publications for gene: CREB3L1 were set to 25007323; 29936144.; 28817112
Skeletal dysplasia v1.194 CREB3L1 Eleanor Williams Classified gene: CREB3L1 as Green List (high evidence)
Skeletal dysplasia v1.194 CREB3L1 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Is Green on the Osteogenesis imperfecta panel and 4 cases reported.
Skeletal dysplasia v1.194 CREB3L1 Eleanor Williams Gene: creb3l1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.193 CREB3L1 Eleanor Williams commented on gene: CREB3L1: 4 cases now reported each in a publication (PMID: 24079343 - whole gene deletion, PMID: 28817112 - 3bp in-frame deletion (c.934_936delAAG [p.Lys312del], PMID: 29936144 - premature stop codon c.1284C>A; p.Tyr428*, PMID: 30657919 - homozygous missense variant (p.(Ala304Val))
Skeletal dysplasia v1.193 ARSE Louise Daugherty Tag new-gene-name tag was added to gene: ARSE.
Skeletal dysplasia v1.193 ARSE Louise Daugherty commented on gene: ARSE
Skeletal dysplasia v1.193 ZIC1 Rhoda Akilapa reviewed gene: ZIC1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniosynostosis; Mode of inheritance: None
Skeletal dysplasia v1.193 TCOF1 Rhoda Akilapa commented on gene: TCOF1
Skeletal dysplasia v1.193 TCF12 Rhoda Akilapa reviewed gene: TCF12: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniosynostosis; Mode of inheritance: None
Skeletal dysplasia v1.193 KAT6A Rhoda Akilapa commented on gene: KAT6A
Skeletal dysplasia v1.193 EFNB1 Rhoda Akilapa commented on gene: EFNB1
Skeletal dysplasia v1.193 LBR Eleanor Williams Added comment: Comment on mode of inheritance: Appears to be Biallelic in Greenberg dysplasia and in Pelger-Huet anomaly with skeletal anomalies. (Pelger-Huet anomaly without skeletal involvement can be monoallelic)
Skeletal dysplasia v1.193 LBR Eleanor Williams Mode of inheritance for gene: LBR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.192 IFT81 Eleanor Williams changed review comment from: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly (c.1188+1G-A). The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed. Only candidate gene sequencing of IFT-B complex proteins was found. A variant in IFT81 (c.2015_2019delACCGG) was also found in a second unrelated child with retinal dystrophy and intellectual disability (no skeletal phenotype) suggestive of a ciliopathy however 9 additional rare homozygous variants were found and so this variant has also been classified as a VUS in OMIM.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

PMID: 30080953 - Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). The duplication was predicted to disrupt the ORF and cause a truncation of the peptide sequence. He had narrow thorax, short arms, brachydactyly and short stature. Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.

Summary - 2 cases with SNVs and strong skeletal phenotype, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype. 4th case with tandem duplication of 2 exons. ; to: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly (c.1188+1G-A). The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed. Only candidate gene sequencing of IFT-B complex proteins was found. A variant in IFT81 (c.2015_2019delACCGG) was also found in a second unrelated child with retinal dystrophy and intellectual disability (no skeletal phenotype) suggestive of a ciliopathy however 9 additional rare homozygous variants were found and so this variant has also been classified as a VUS in OMIM.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

PMID: 30080953 - Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). The duplication was predicted to disrupt the ORF and cause a truncation of the peptide sequence. He had narrow thorax, short arms, brachydactyly and short stature. Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.

Summary - 2 cases with SNVs and strong skeletal phenotype, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype and the variant classified as a VUS. 4th case with tandem duplication of 2 exons which is predicted to result in a truncated protein.
Skeletal dysplasia v1.192 IFT81 Eleanor Williams changed review comment from: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

PMID: 30080953 - Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). The duplication was predicted to disrupt the ORF and cause a truncation of the peptide sequence. He had narrow thorax, short arms, brachydactyly and short stature. Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.

Summary - 2 cases with SNVs and strong skeletal phenotype, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype. 4th case with tandem duplication of 2 exons. ; to: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly (c.1188+1G-A). The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed. Only candidate gene sequencing of IFT-B complex proteins was found. A variant in IFT81 (c.2015_2019delACCGG) was also found in a second unrelated child with retinal dystrophy and intellectual disability (no skeletal phenotype) suggestive of a ciliopathy however 9 additional rare homozygous variants were found and so this variant has also been classified as a VUS in OMIM.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

PMID: 30080953 - Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). The duplication was predicted to disrupt the ORF and cause a truncation of the peptide sequence. He had narrow thorax, short arms, brachydactyly and short stature. Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.

Summary - 2 cases with SNVs and strong skeletal phenotype, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype. 4th case with tandem duplication of 2 exons.
Skeletal dysplasia v1.192 IFT81 Eleanor Williams changed review comment from: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

PMID: 30080953 - Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). He had narrow thorax, short arms, brachydactyly and short stature. Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.

Summary - 2 cases with SNVs and strong skeletal phenotype, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype. 4th case with tandem duplication of 2 exons. ; to: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

PMID: 30080953 - Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). The duplication was predicted to disrupt the ORF and cause a truncation of the peptide sequence. He had narrow thorax, short arms, brachydactyly and short stature. Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.

Summary - 2 cases with SNVs and strong skeletal phenotype, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype. 4th case with tandem duplication of 2 exons.
Skeletal dysplasia v1.192 IFT81 Eleanor Williams changed review comment from: Additional publication - PMID: 30080953 Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.; to: Additional publication - PMID: 30080953 Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). The duplication was predicted to disrupt the ORF and cause a truncation of the peptide sequence. Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.
Skeletal dysplasia v1.192 B9D1 Eleanor Williams changed review comment from: Associated with ?Meckel syndrome 9 (#614209) and Joubert syndrome 27 (#617120) in OMIM.
Gene2Phenotype reports a probable association with MECKEL SYNDROME 9.

PMID: 24886560 - Romani et al 2014 - report mutations in B9D1 in two patients, a 9-year-old boy (COR363) and a 7-year-old girl (COR346), both presenting with pure JS. The mutations (cG467A; p.R156Q homo, and cA95G; p.Y32C, c.520-522delGTG; p.V175del) were inherited from heterozygous healthy parents, were not reported in public databases, and affected highly conserved residues. Missense mutations were predicted as pathogenic by prediction web tools. Neither patient showed polydactyly or orofacial features although patient COR363's facial dysmorphisms included a triangular face, retrognatism, accentuated philtrum and big ears, and patient COR346's dysmorphic facial features included frontal bossing, macrostomia, thick lips and low-set ears.

PMID: 21493627 - Hopp et al 2011 - In family M456 with Meckel syndrome (MKS), a splice-donor site change in B9D1 was detected in a fetus (c.505+2T>C). Sanger sequencing revealed likely hemizygosity of this variant, with a de novo deletion of the B9D1 locus in the fetus. The deletion spans 1.713 Mb at chromosome 17p11.2, including the complete B9D1 locus. Additionally, 18 other genes were deleted. The authors also identified a novel change in a second MKS gene, CEP290. Sanger sequencing showed that the heterozygous variant, p.R2210C, was inherited from the mother.
Polydactyly, that is typical in MKS, was not noted but the fetus had bilateral club feet and shortened limbs.; to: Associated with ?Meckel syndrome 9 (#614209) and Joubert syndrome 27 (#617120) in OMIM.
Gene2Phenotype reports a probable association with MECKEL SYNDROME 9.

PMID: 24886560 - Romani et al 2014 - report mutations in B9D1 in two unrelated patients, a 9-year-old boy (COR363) and a 7-year-old girl (COR346), both presenting with pure JS. The mutations (cG467A; p.R156Q homo, and cA95G; p.Y32C, c.520-522delGTG; p.V175del) were inherited from heterozygous healthy parents, were not reported in public databases, and affected highly conserved residues. Missense mutations were predicted as pathogenic by prediction web tools. Neither patient showed polydactyly or orofacial features although patient COR363's facial dysmorphisms included a triangular face, retrognatism, accentuated philtrum and big ears, and patient COR346's dysmorphic facial features included frontal bossing, macrostomia, thick lips and low-set ears.

PMID: 21493627 - Hopp et al 2011 - In family M456 with Meckel syndrome (MKS), a splice-donor site change in B9D1 was detected in a fetus (c.505+2T>C). Sanger sequencing revealed likely hemizygosity of this variant, with a de novo deletion of the B9D1 locus in the fetus. The deletion spans 1.713 Mb at chromosome 17p11.2, including the complete B9D1 locus. Additionally, 18 other genes were deleted. The authors also identified a novel change in a second MKS gene, CEP290. Sanger sequencing showed that the heterozygous variant, p.R2210C, was inherited from the mother.
Polydactyly, that is typical in MKS, was not noted but the fetus had bilateral club feet and shortened limbs.
Skeletal dysplasia v1.192 MMP9 Eleanor Williams changed review comment from: Associated with Metaphyseal anadysplasia 2 (613073) in OMIM

PMID: 19615667 - Lausch et al 2009 - 1 family. In a recessive kindred, family E, MMP13 was normal, but a c.21T>A transversion in exon 1 altered the start codon of MMP9, substituting methionine with lysine. The variant segregated with the disease in the family.

PMID: 28342220 - Sharony et al 2017 - 1 family. Two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses. NM_004994: c.[559C>T], p.(L187F).

PMID: 24781753 - Li et al 2015 - 0 families. 2 brothers with short stature and mixed epiphyseal and metaphyseal dysplasia. Identified a homozygous C>T transition mutation in exon 2 of MMP13 (c.325C>T, p.(R109*). So not in MMP9.

Only 2 cases reported, 3rd had variant in MMP13 not MMP9.

Mouse model - PMID: 9590175 - Vu et al. 1998 - report that homozygous mice with a null mutation in the MMP-9/gelatinase B gene exhibit an abnormal pattern of skeletal growth plate vascularization and ossification.; to: Associated with Metaphyseal anadysplasia 2 (613073) in OMIM

PMID: 19615667 - Lausch et al 2009 - 1 family. In a recessive kindred, family E, MMP13 was normal, but a c.21T>A transversion in exon 1 altered the start codon of MMP9, substituting methionine with lysine. The variant segregated with the disease in the family.

PMID: 28342220 - Sharony et al 2017 - 1 family. Two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses. NM_004994: c.[559C>T], p.(L187F).

PMID: 24781753 - Li et al 2015 - 0 families. 2 brothers with short stature and mixed epiphyseal and metaphyseal dysplasia. Identified a homozygous C>T transition mutation in exon 2 of MMP13 (c.325C>T, p.(R109*). So not in MMP9.

Summary: only 2 cases reported, 3rd had variant in MMP13 not MMP9.

Mouse model - PMID: 9590175 - Vu et al. 1998 - report that homozygous mice with a null mutation in the MMP-9/gelatinase B gene exhibit an abnormal pattern of skeletal growth plate vascularization and ossification.
Skeletal dysplasia v1.192 NIN Zornitza Stark reviewed gene: NIN: Rating: RED; Mode of pathogenicity: None; Publications: 22933543, 23665482; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.192 WDR19 Eleanor Williams changed review comment from: PMID: 22019273 - Bredrup et al. (2011) - 2 cases. Case 1 - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Case 2 - They also found a a Dutch patient (previously described in Vries et al, 2010) with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .

3 cases in total.; to: PMID: 22019273 - Bredrup et al. (2011) - 2 cases. Case 1 - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Case 2 - They also found a a Dutch patient (previously described in Vries et al, 2010) with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies (such as right-convex scoliosis and congenital hip dysplasia), strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .

3 cases in total.
Skeletal dysplasia v1.192 WDR19 Eleanor Williams changed review comment from: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient (previously described in Vries et al, 2010) with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .

3 cases in total.; to: PMID: 22019273 - Bredrup et al. (2011) - 2 cases. Case 1 - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Case 2 - They also found a a Dutch patient (previously described in Vries et al, 2010) with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .

3 cases in total.
Skeletal dysplasia v1.192 NIN Eleanor Williams changed review comment from: PMID: 22933543 - Dauber et al. (2012) -2 sisters with severe short stature, microcephaly, and developmental delay (Seckel syndrome-7) were identified to have compound heterozygosity for missense mutations in the NIN gene (Q1222R; N1709S)

PMID: 23665482 -Grosch et al (2013) - in a consanguineous family with a phenotype resembling Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) they identified homozygous missense mutations in the two nearby genes NIN and POLE2 which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. They present evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype. The NIN variant is classified as a VUS in OMIM. ; to: PMID: 22933543 - Dauber et al. (2012) -2 sisters with severe short stature, microcephaly, and developmental delay (Seckel syndrome-7) were identified to have compound heterozygosity for missense mutations in the NIN gene (Q1222R; N1709S). The p.N1709S is a novel variant that is not present in Single Nucleotide Polymorphism database, 1000 Genomes pilot data, or the NHLBI exome variant server. The p.Q1222R was present only in the 1000 Genomes pilot data with an overall minor allele frequency of 0.001 (0.005 in the Americas subcohort). In patient derived primary dermal fibroblasts, the compound heterozygous NIN defects did not disrupt Ninein expression or localization or obviously affect mitotic functions. But zebrafish nin morphilino knockdowns include phenotypes such as reduced growth and altered patterning of the skull, consistent with general phenotypic characteristics of MPD.

PMID: 23665482 -Grosch et al (2013) - in a consanguineous family with a phenotype resembling Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) they identified homozygous missense mutations in the two nearby genes NIN and POLE2 which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. They present evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype. The NIN variant is classified as a VUS in OMIM.
Skeletal dysplasia v1.192 IFT43 Eleanor Williams changed review comment from: Associated with ?Cranioectodermal dysplasia 3 (#614099) and Short-rib thoracic dysplasia 18 with polydactyly (#617866) in OMIM and with CRANIOECTODERMAL DYSPLASIA TYPE 3 (confirmed) in Gene2Phenotype.

PMID: 21378380- Arts et al. 2011 - 1 case . 2 siblings from a consanguineous family of Moroccan descent with cranioectodermal dysplasia (Sensenbrenner syndrome). The reported phenotype includes Rhizomelic shortening of limbs, narrow thorax, toe syndactyly, brachydactyly, and polydactyly (one sibling). Following genome-wide homozygosity mapping two candidate genes were analyzed and a homozygous missense mutation in the translation initiation codon of the IFT43 gene was identified. Fibroblasts from one of the affected siblings (II:2) show a typical IFT-A defect (ie, accumulation of IFT-B complex proteins in the ciliary tip.

PMID: 28400947 - Duran et al. 2017- 2 cases - in 3 affected individuals from 2 unrelated families with short-rib thoracic dysplasia with polydactyly thye identified homozygosity for missense mutations in the IFT143 gene, M1K and W179R.

PMID: 26892345 - Stokman et al 2016 - 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. They de novo 4.5-Mb microdeletion which contains 65 protein-coding genes, including the ciliary gene IFT43. Immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport.; to: Associated with ?Cranioectodermal dysplasia 3 (#614099) and Short-rib thoracic dysplasia 18 with polydactyly (#617866) in OMIM and with CRANIOECTODERMAL DYSPLASIA TYPE 3 (confirmed) in Gene2Phenotype.

PMID: 21378380- Arts et al. 2011 - 1 case . 2 siblings from a consanguineous family of Moroccan descent with cranioectodermal dysplasia (Sensenbrenner syndrome). The reported phenotype includes Rhizomelic shortening of limbs, narrow thorax, toe syndactyly, brachydactyly, and polydactyly (one sibling). Following genome-wide homozygosity mapping two candidate genes were analyzed and a homozygous missense mutation in the translation initiation codon of the IFT43 gene was identified. Fibroblasts from one of the affected siblings (II:2) show a typical IFT-A defect (ie, accumulation of IFT-B complex proteins in the ciliary tip.

PMID: 28400947 - Duran et al. 2017- 2 cases - in 3 affected individuals from 2 unrelated families with short-rib thoracic dysplasia with polydactyly they identified homozygosity for missense mutations in the IFT143 gene, M1K and W179R.

PMID: 26892345 - Stokman et al 2016 - 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. They de novo 4.5-Mb microdeletion which contains 65 protein-coding genes, including the ciliary gene IFT43. Immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport.
Skeletal dysplasia v1.192 GZF1 Eleanor Williams Classified gene: GZF1 as Green List (high evidence)
Skeletal dysplasia v1.192 GZF1 Eleanor Williams Gene: gzf1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Deleted their comment
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Classified gene: GZF1 as Amber List (moderate evidence)
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Added comment: Comment on list classification: Demoting from Green to Amber as a result of expert review. Only 2 cases although there is some functional evidence supporting the role of this protein in the disease.
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Gene: gzf1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.190 GPX4 Eleanor Williams Classified gene: GPX4 as Amber List (moderate evidence)
Skeletal dysplasia v1.190 GPX4 Eleanor Williams Added comment: Comment on list classification: Demoting from Green to Amber. 3 variants but only 2 cases.
Skeletal dysplasia v1.190 GPX4 Eleanor Williams Gene: gpx4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.189 B9D1 Eleanor Williams Classified gene: B9D1 as Amber List (moderate evidence)
Skeletal dysplasia v1.189 B9D1 Eleanor Williams Added comment: Comment on list classification: Demoting from Green to Amber, as the association with a skeletal phenotype is not clear.
Skeletal dysplasia v1.189 B9D1 Eleanor Williams Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.188 ADAMTS17 Eleanor Williams Classified gene: ADAMTS17 as Green List (high evidence)
Skeletal dysplasia v1.188 ADAMTS17 Eleanor Williams Added comment: Comment on list classification: More than 3 cases reported with patients with short stature.
Skeletal dysplasia v1.188 ADAMTS17 Eleanor Williams Gene: adamts17 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.187 ADAMTS17 Eleanor Williams Publications for gene: ADAMTS17 were set to
Skeletal dysplasia v1.186 ADAMTS17 Eleanor Williams Mode of inheritance for gene: ADAMTS17 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.185 RAB33B Eleanor Williams Publications for gene: RAB33B were set to
Skeletal dysplasia v1.184 RAB33B Eleanor Williams Classified gene: RAB33B as Green List (high evidence)
Skeletal dysplasia v1.184 RAB33B Eleanor Williams Added comment: Comment on list classification: 5 cases reported.
Skeletal dysplasia v1.184 RAB33B Eleanor Williams Gene: rab33b has been classified as Green List (High Evidence).
Skeletal dysplasia v1.183 PAM16 Eleanor Williams Classified gene: PAM16 as Amber List (moderate evidence)
Skeletal dysplasia v1.183 PAM16 Eleanor Williams Added comment: Comment on list classification: 3 cases, but two are likely to share the same founder mutation. Rating amber until further cases are reported.
Skeletal dysplasia v1.183 PAM16 Eleanor Williams Gene: pam16 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.182 PAM16 Eleanor Williams changed review comment from: Associated with Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type (#613320) in OMIM.

PMID: 27354339 - Moosa et al 2016 - 1 patient with a spondylometaphyseal dysplasia, most closely resembling odontochondrodysplasi. A homozygous c.221A>C (p.Q74P) mutation in PAM16, which was not present in the ExAC database was identified.

PMID: 24786642 - Mehawej et al 2014 - Two unrelated consanguineous Lebanese families with four affected cases presenting a novel type of early lethal spondylodysplastic dysplasia. Identified c.226A>G transition in MAGMAS (PAM16) to segregated with the disease in both families. The mutation was homozygous in the patients, heterozygous in the parents and in the unaffected sibs in both families. Likely founder mutation.
Show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein.; to: Associated with Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type (#613320) in OMIM.

PMID: 27354339 - Moosa et al 2016 - 1 patient with distantly related Argentinian parents of central European descent, with a spondylometaphyseal dysplasia, most closely resembling odontochondrodysplasi. A homozygous c.221A>C (p.Q74P) mutation in PAM16, which was not present in the ExAC database was identified.

PMID: 24786642 - Mehawej et al 2014 - Two unrelated consanguineous Lebanese families with four affected cases presenting a novel type of early lethal spondylodysplastic dysplasia. Identified c.226A>G transition in MAGMAS (PAM16) to segregated with the disease in both families. The mutation was homozygous in the patients, heterozygous in the parents and in the unaffected sibs in both families. Likely founder mutation.
Show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein.
Skeletal dysplasia v1.182 PAM16 Eleanor Williams changed review comment from: PMID: 27354339 - Moosa et al 2016 - 1 patient with a spondylometaphyseal dysplasia, most closely resembling odontochondrodysplasi. A homozygous c.221A>C (p.Q74P) mutation in PAM16, which was not present in the ExAC database was identified.

PMID: 24786642 - Mehawej et al 2014 - Two unrelated consanguineous Lebanese families with four affected cases presenting a novel type of early lethal spondylodysplastic dysplasia. Identified c.226A>G transition in MAGMAS (PAM16) to segregated with the disease in both families. The mutation was homozygous in the patients, heterozygous in the parents and in the unaffected sibs in both families. Likely founder mutation.
Show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein.; to: Associated with Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type (#613320) in OMIM.

PMID: 27354339 - Moosa et al 2016 - 1 patient with a spondylometaphyseal dysplasia, most closely resembling odontochondrodysplasi. A homozygous c.221A>C (p.Q74P) mutation in PAM16, which was not present in the ExAC database was identified.

PMID: 24786642 - Mehawej et al 2014 - Two unrelated consanguineous Lebanese families with four affected cases presenting a novel type of early lethal spondylodysplastic dysplasia. Identified c.226A>G transition in MAGMAS (PAM16) to segregated with the disease in both families. The mutation was homozygous in the patients, heterozygous in the parents and in the unaffected sibs in both families. Likely founder mutation.
Show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein.
Skeletal dysplasia v1.182 PAM16 Eleanor Williams changed review comment from: This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: PAM16; Initial rating suggestion: green; to: This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: PAM16; Initial rating suggestion: green
Skeletal dysplasia v1.182 MMP9 Eleanor Williams changed review comment from: Associated with Metaphyseal anadysplasia 2 (613073) in OMIM

PMID: 19615667 - Lausch et al 2009 - 1 family. In a recessive kindred, family E, MMP13 was normal, but a c.21T>A transversion in exon 1 altered the start codon of MMP9, substituting methionine with lysine. The variant segregated with the disease in the family.

PMID: 28342220 - Sharony et al 2017 - 1 family. Two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses. NM_004994: c.[559C>T], p.(L187F).

PMID: 24781753 - Li et al 2015 - 0 families. 2 brothers with short stature and mixed epiphyseal and metaphyseal dysplasia. Identified a homozygous C>T transition mutation in exon 2 of MMP13 (c.325C>T, p.(R109*). So not in MMP9.

Only 2 cases reported, 3rd had variant in MMP13 not MMP9.; to: Associated with Metaphyseal anadysplasia 2 (613073) in OMIM

PMID: 19615667 - Lausch et al 2009 - 1 family. In a recessive kindred, family E, MMP13 was normal, but a c.21T>A transversion in exon 1 altered the start codon of MMP9, substituting methionine with lysine. The variant segregated with the disease in the family.

PMID: 28342220 - Sharony et al 2017 - 1 family. Two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses. NM_004994: c.[559C>T], p.(L187F).

PMID: 24781753 - Li et al 2015 - 0 families. 2 brothers with short stature and mixed epiphyseal and metaphyseal dysplasia. Identified a homozygous C>T transition mutation in exon 2 of MMP13 (c.325C>T, p.(R109*). So not in MMP9.

Only 2 cases reported, 3rd had variant in MMP13 not MMP9.

Mouse model - PMID: 9590175 - Vu et al. 1998 - report that homozygous mice with a null mutation in the MMP-9/gelatinase B gene exhibit an abnormal pattern of skeletal growth plate vascularization and ossification.
Skeletal dysplasia v1.182 MMP9 Eleanor Williams Publications for gene: MMP9 were set to 28342220; 24781753; 19615667
Skeletal dysplasia v1.181 MMP9 Eleanor Williams Classified gene: MMP9 as Amber List (moderate evidence)
Skeletal dysplasia v1.181 MMP9 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber as two cases have been reported with variants in this gene.
Skeletal dysplasia v1.181 MMP9 Eleanor Williams Gene: mmp9 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.180 MATN3 Eleanor Williams Publications for gene: MATN3 were set to
Skeletal dysplasia v1.179 MATN3 Eleanor Williams Classified gene: MATN3 as Green List (high evidence)
Skeletal dysplasia v1.179 MATN3 Eleanor Williams Added comment: Comment on list classification: More than 3 cases of variants in this gene in patients with a relevant phenotype.
Skeletal dysplasia v1.179 MATN3 Eleanor Williams Gene: matn3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.178 MATN3 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving mode of inheritance as monoallelelic, as only one case reported of biallelic variants causing Spondyloepimetaphyseal Dysplasia so far.
Skeletal dysplasia v1.178 MATN3 Eleanor Williams Mode of inheritance for gene: MATN3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.177 MATN3 Eleanor Williams changed review comment from: Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.

Epiphyseal dysplasia:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).

Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.

Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.; to: Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.

Epiphyseal dysplasia:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).
PMID: PMID: 30080953 - Pettersson et al 2018 - in a 17‐year‐old girl born to healthy, nonconsanguineous parents of Caucasian origin who was diagnosed with multiple epiphyseal dysplasia they identified a heterozygous intragenic duplication within MATN3, affecting exons 2–5 by custom array‐CGH.

Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.

Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.
Skeletal dysplasia v1.177 MATN3 Eleanor Williams changed review comment from: Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.

Epiphyseal dysplasia including:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).

Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.

Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.; to: Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.

Epiphyseal dysplasia:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).

Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.

Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.
Skeletal dysplasia v1.177 MATN3 Eleanor Williams commented on gene: MATN3: Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.

Epiphyseal dysplasia including:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).

Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.

Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.
Skeletal dysplasia v1.177 FZD2 Eleanor Williams Classified gene: FZD2 as Green List (high evidence)
Skeletal dysplasia v1.177 FZD2 Eleanor Williams Added comment: Comment on list classification: More than 3 cases with variants in FZD2 in patients with a relevant phenotype.
Skeletal dysplasia v1.177 FZD2 Eleanor Williams Gene: fzd2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.176 FZD2 Eleanor Williams changed review comment from: Associated with Omodysplasia 2 (164745) in OMIM.

PMID: 25759469 - Saal et al 2015 - 1 family. proband with omodysplasia, her unaffected parents and her affected daughter. Identified a de novo mutation (c.1644G>A, p.Trp548*) in FZD2 in the proband and her daughter that was not found in unaffected family members. Show reduced ability of this mutant form of FZD2 to interact with its downstream target DISHEVELLED. Furthermore, expressing the mutant form of FZD2 in vitro is not able to facilitate the cellular response to canonical Wnt signaling like wild-type FZD2.

PMID: 29230162 - Türkmen et al 2017 - 1 patient. A heterozygous de novo mutation (G434V) in the frizzled class receptor 2 (FZD2) gene in a patient with distinct facial features including hypertelorism, bilateral cleft lip/palate, short nose with a broad nasal bridge, microretrognathia, and bilateral shortness of the upper limbs, first metacarpal bones, and middle phalanges of the 5th digits.

PMID: 29383830 - invalid pubmed id

PMID: 29383834 - Nagasaki et al 2018 - 1 patient. 16-year-old boy with OMOD2 or Robinow syndrome-like phenotype. Molecular analysis identified a de novo, heterozygous, nonsense mutation (c.1640C>A, p.S547*) in FZD2.

PMID: 30455931 - Warren et al 2018 - 2 patients. Presented are two patients with autosomal dominant omodysplasia and mutations in the FZD2 gene. The mutations identified have been recently reported, suggesting the possibility of recurrent mutations. The phenotypes of these patients overlap with what has been previously reported, though intellectual disability as seen in our patient is not typical.

Total of 4 cases; to: Associated with Omodysplasia 2 (164745) in OMIM.

PMID: 25759469 - Saal et al 2015 - 1 family. proband with omodysplasia, her unaffected parents and her affected daughter. Identified a de novo mutation (c.1644G>A, p.Trp548*) in FZD2 in the proband and her daughter that was not found in unaffected family members. Show reduced ability of this mutant form of FZD2 to interact with its downstream target DISHEVELLED. Furthermore, expressing the mutant form of FZD2 in vitro is not able to facilitate the cellular response to canonical Wnt signaling like wild-type FZD2.

PMID: 29230162 - Türkmen et al 2017 - 1 patient. A heterozygous de novo mutation (G434V) in the frizzled class receptor 2 (FZD2) gene in a patient with distinct facial features including hypertelorism, bilateral cleft lip/palate, short nose with a broad nasal bridge, microretrognathia, and bilateral shortness of the upper limbs, first metacarpal bones, and middle phalanges of the 5th digits.

PMID: 29383830 - invalid pubmed id

PMID: 29383834 - Nagasaki et al 2018 - 1 patient. 16-year-old boy with OMOD2 or Robinow syndrome-like phenotype. Molecular analysis identified a de novo, heterozygous, nonsense mutation (c.1640C>A, p.S547*) in FZD2.

PMID: 30455931 - Warren et al 2018 - 2 patients. Presented are two patients with autosomal dominant omodysplasia and mutations in the FZD2 gene. Patient 1 has a p.Trp548* alteration previously reported. Patient 2 has missense alteration p.Gly434Val also previously reported. The phenotypes of these patients overlap with what has been previously reported, though patient 2 also presented with intellectual disability which is not typical.

Total of 4 cases
Skeletal dysplasia v1.176 FN1 Eleanor Williams Added comment: Comment on mode of pathogenicity: Only missense or inframe deletions reported to date.
Skeletal dysplasia v1.176 FN1 Eleanor Williams Mode of pathogenicity for gene: FN1 was changed from to Other
Skeletal dysplasia v1.175 FN1 Eleanor Williams Classified gene: FN1 as Green List (high evidence)
Skeletal dysplasia v1.175 FN1 Eleanor Williams Added comment: Comment on list classification: More than 3 cases reported of plausible disease causing mutations found in the FN1 gene in patients with a relevant phenotype.
Skeletal dysplasia v1.175 FN1 Eleanor Williams Gene: fn1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.174 FN1 Eleanor Williams Publications for gene: FN1 were set to 29100092
Skeletal dysplasia v1.173 FN1 Eleanor Williams Mode of inheritance for gene: FN1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.172 FN1 Eleanor Williams commented on gene: FN1: This gene is associated with Spondylometaphyseal dysplasia, corner fracture type (#184255) in OMIM.

PMID: 29100092 - Lee et al 2017 - 7 cases. Variants in FN1 found in patients from 7 families with Spondylometaphyseal dysplasias with corner fractures. 2 cases were familial, the rest were de novo mutations. In the two familial cases inheritance was autosomal dominant. All FN1 variants discovered in this study are absent from the ExAC Browser and affect highly conserved residues. 6 of the variants were missense, and one was an inframe deletion.

PMID: 30599297 - Costantini et al 2019 - 5 cases. Using WGS/WES or targeted Sanger sequencing they identified 5 heterozygous missense variants in FN1 in patients with spondylometaphyseal dysplasia with "corner fractures" (SMD-CF). In two families the variant was inherited from an affected parent. None of the patients had impaired renal function.
Skeletal dysplasia v1.172 ADAMTS17 Eleanor Williams commented on gene: ADAMTS17: Associated with Weill-Marchesani 4 syndrome, recessive #613195 in OMIM. This condition is characterized by short stature and brachydactyly as well as eye-associated clinical features.

PMID: 19836009 - Morales et al. 2009 - 3 cases from Saudi Arabia, 2 familial and 1 sporadic. 7 affected individuals. All had short stature and ocular manifestations but not brachydactyly so are described as WMS-like. 3 different homozygous variants were detected (1 bp insertion, a splice-site mutation, and a nonsense mutation).

PMID: 22486325 - Khan et al. 2012 - 1 case. A sister and brother with WMS from a consanguineous Saudi family were found to have a 1-bp deletion that segregated with disease. The probands presented with high myopia and had spherophakia. Although both had short stature, neither had short hands, short feet, joint stiffness, or non-ocular congenital abnormalities

PMID: 24940034 - Shah et al. 2014 - 1 case. In an Indian family WES analysis identified a homozygous novel splice-site mutation c.873+1G>T in ADAMTS1 in a 21 year old proband. RT-PCR analysis in the patient showed that exon 5 was skipped, which resulted in the deletion of 28 amino acids in the ADAMTS17 protein. The proband presented with decreased vision. She had short stature, brachydactyly, but no joint stiffness.

PMID: 31019231 - Yi et al 2019 - 1 case. In a consanguineous Chinese family, a nonsense mutation c.1051 A > T in ADAMTS17 was identified. (Abstract only accessed).

More than 3 cases. Short stature reported but brachydactyly only in 1 case.
Skeletal dysplasia v1.172 ADAMTS10 Eleanor Williams Phenotypes for gene: ADAMTS10 were changed from Weill-Marchesani syndrome type 1 to Weill-Marchesani syndrome 1, recessive, 277600
Skeletal dysplasia v1.171 ADAMTS10 Eleanor Williams Publications for gene: ADAMTS10 were set to
Skeletal dysplasia v1.170 ADAMTS10 Eleanor Williams Mode of inheritance for gene: ADAMTS10 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.169 ADAMTS10 Eleanor Williams Classified gene: ADAMTS10 as Green List (high evidence)
Skeletal dysplasia v1.169 ADAMTS10 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as there are more than 3 cases with variants in ADAMS10 in patients with Weill-Marchesani syndrome. Plus a mouse model with a WMS associated truncating mutation has a skeletal phenotype.
Skeletal dysplasia v1.169 ADAMTS10 Eleanor Williams Gene: adamts10 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.168 ADAMTS10 Eleanor Williams commented on gene: ADAMTS10: Associated with Weill-Marchesani syndrome 1, recessive (#277600) in OMIM.

PMID: 15368195 - Dagoneau et al. 2004 - 3 cases. following homozygosity-mapping strategy in two consanguineous families from Lebanon and Saudi Arabia with Weill-Marchesani syndrome they selected ADAMTS10 for further sequencing. They found three distinct mutations of the ADAMTS10 gene in these two families and in one sporadic WMS case (one nonsense mutation (R237X) and two splice-site mutations). The variants segregated with the disease in the familial cases. All probands fulfilled the criteria for WMS with short stature, brachydactyly, limitation of joint movement, microspherophakia, dislocated lenses, severe myopia, and glaucoma.

PMID: 19836009 - Morales et al. 2009 - 2 cases. Two families which met the diagnostic criteria for WMS were each found to have a different homozygous missense mutation in ADAMTS10 (c.1553 G > A (p.G518D) and c.2098 G > T (p.G700C)).

PMID: 30060141 - Mularczyk et al 2018 - A mouse model containing a truncation mutation on ADAMS10 seen in WMS patients was created. Homozygous WMS mice are smaller and have shorter long bones with perturbation to the zones of the developing growth plate and changes in cell proliferation.
Skeletal dysplasia v1.168 WDR19 Eleanor Williams changed review comment from: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .; to: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient (previously described in Vries et al, 2010) with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .

3 cases in total.
Skeletal dysplasia v1.168 WDR19 Eleanor Williams changed review comment from: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient with Jeune syndrome and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .; to: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .
Skeletal dysplasia v1.168 TMEM67 Eleanor Williams changed review comment from: Associated with several phenotypes in OMIM but ?RHYNS syndrome (#609884) is the main disease phenotype that has a skeletal component. Polydactyly may also be seen in Meckel syndrome 3 (#607361).

RHYNS syndrome - 1 case

PMID: 9375913 - Di Rocco et al. (1997) - 1 case. 17.5-year-old boy with short stature, severe bone-age retardation and exhibited mild signs of skeletal dysplasia, including generalized osteopenia, epiphyseal hypoplasia, hypoplastic iliac bones with irregular acetabular margins, and thin tubular bones. He later developed nephronophthisis. Brancati et al. (2018) (PMID: 29891882) re-assessed this patient at age 38 years and reported he exhibited short stature and severe generalized osteoporosis. Skeletal survey showed moderately shortened long bones, bowed radii, short femoral neck, brachydactyly of the hands and feet with more severe involvement of middle phalanges, distal phalanx of the thumbs, and metacarpals, moderately thickened calvarium, and rotoscoliosis. Compound heterozygous variants in TMEM67 were identified, one inherited from each of his parents.

PMID: 11391657 - Hedera and Gorski (2001) described 2 brothers, who had early onset retinitis pigmentosa, short stature with GH deficiency, mild facial asymmetry, and acromelic shortening of the distal extremities. They suggest this phenotype is consistent with RHYNS syndrome but no genome analysis was done.

Meckel syndrome 3
PMID: 16415887 - Smith et al. 2006 - detected 5 different homozygous mutations in the TMEM67 in 5 consanguineous families with Meckel syndrome. The mutations were not found in over 120 ethnically matched normal control chromosomes. Polydactyly was observed in 2 out of the 5 families.

PMID: 17377820 - Consugar et al. 2007 - identified 7 novel pathogenic mutations in the TMEM67 gene in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All cases were compound heterogygous. Polydactyly is reported in 1 family.; to: Associated with several phenotypes in OMIM but ?RHYNS syndrome (#609884) is the main disease phenotype that has a skeletal component. Polydactyly may also be seen in Meckel syndrome 3 (#607361).

RHYNS syndrome - 1 case:

PMID: 9375913 - Di Rocco et al. (1997) - 1 case. 17.5-year-old boy with short stature, severe bone-age retardation and exhibited mild signs of skeletal dysplasia, including generalized osteopenia, epiphyseal hypoplasia, hypoplastic iliac bones with irregular acetabular margins, and thin tubular bones. He later developed nephronophthisis. Brancati et al. (2018) (PMID: 29891882) re-assessed this patient at age 38 years and reported he exhibited short stature and severe generalized osteoporosis. Skeletal survey showed moderately shortened long bones, bowed radii, short femoral neck, brachydactyly of the hands and feet with more severe involvement of middle phalanges, distal phalanx of the thumbs, and metacarpals, moderately thickened calvarium, and rotoscoliosis. Compound heterozygous variants in TMEM67 were identified, one inherited from each of his parents.

PMID: 11391657 - Hedera and Gorski (2001) described 2 brothers, who had early onset retinitis pigmentosa, short stature with GH deficiency, mild facial asymmetry, and acromelic shortening of the distal extremities. They suggest this phenotype is consistent with RHYNS syndrome but no genome analysis was done.

Meckel syndrome 3 - 3 out of 22 cases show polydactyly:

PMID: 16415887 - Smith et al. 2006 - detected 5 different homozygous mutations in the TMEM67 in 5 consanguineous families with Meckel syndrome. The mutations were not found in over 120 ethnically matched normal control chromosomes. Polydactyly was observed in 2 out of the 5 families.

PMID: 17377820 - Consugar et al. 2007 - identified 7 novel pathogenic mutations in the TMEM67 gene in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All cases were compound heterogygous. Polydactyly is reported in 1 family.
Skeletal dysplasia v1.168 TMEM67 Eleanor Williams commented on gene: TMEM67: Associated with several phenotypes in OMIM but ?RHYNS syndrome (#609884) is the main disease phenotype that has a skeletal component. Polydactyly may also be seen in Meckel syndrome 3 (#607361).

RHYNS syndrome - 1 case

PMID: 9375913 - Di Rocco et al. (1997) - 1 case. 17.5-year-old boy with short stature, severe bone-age retardation and exhibited mild signs of skeletal dysplasia, including generalized osteopenia, epiphyseal hypoplasia, hypoplastic iliac bones with irregular acetabular margins, and thin tubular bones. He later developed nephronophthisis. Brancati et al. (2018) (PMID: 29891882) re-assessed this patient at age 38 years and reported he exhibited short stature and severe generalized osteoporosis. Skeletal survey showed moderately shortened long bones, bowed radii, short femoral neck, brachydactyly of the hands and feet with more severe involvement of middle phalanges, distal phalanx of the thumbs, and metacarpals, moderately thickened calvarium, and rotoscoliosis. Compound heterozygous variants in TMEM67 were identified, one inherited from each of his parents.

PMID: 11391657 - Hedera and Gorski (2001) described 2 brothers, who had early onset retinitis pigmentosa, short stature with GH deficiency, mild facial asymmetry, and acromelic shortening of the distal extremities. They suggest this phenotype is consistent with RHYNS syndrome but no genome analysis was done.

Meckel syndrome 3
PMID: 16415887 - Smith et al. 2006 - detected 5 different homozygous mutations in the TMEM67 in 5 consanguineous families with Meckel syndrome. The mutations were not found in over 120 ethnically matched normal control chromosomes. Polydactyly was observed in 2 out of the 5 families.

PMID: 17377820 - Consugar et al. 2007 - identified 7 novel pathogenic mutations in the TMEM67 gene in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All cases were compound heterogygous. Polydactyly is reported in 1 family.
Skeletal dysplasia v1.168 RBPJ Eleanor Williams Publications for gene: RBPJ were set to 28160419; 22883147
Skeletal dysplasia v1.167 RBPJ Eleanor Williams changed review comment from: PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ. They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation; to: PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ. They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. All 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation
Skeletal dysplasia v1.167 RBPJ Eleanor Williams changed review comment from: PMID: 22883147 - Hassed et al. [2012] identified mutations in RBPJ through exome sequencing in two independent kindreds with autosomal dominant AOS.

PMID: 28160419 - Hassad et al 2017 - don't think they report any new families.; to: PMID: 22883147 - Hassed et al. 2012 - identified mutations in RBPJ through exome sequencing in two independent kindreds with autosomal dominant AOS.

PMID: 28160419 - Hassad et al 2017 - don't think they report any new families.
Skeletal dysplasia v1.167 RBPJ Eleanor Williams changed review comment from: PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ) They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation; to: PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ. They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation
Skeletal dysplasia v1.167 RBPJ Eleanor Williams changed review comment from: PMID: 29924900 - Meester et al 2018 - analyzed cohort comprised 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ) They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation; to: PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ) They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation
Skeletal dysplasia v1.167 RBPJ Eleanor Williams commented on gene: RBPJ: PMID: 29924900 - Meester et al 2018 - analyzed cohort comprised 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ) They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation
Skeletal dysplasia v1.167 NIN Eleanor Williams changed review comment from: PMID: 22933543 - Dauber et al. (2012) -2 sisters with severe short stature, microcephaly, and developmental delay (Seckel syndrome-7) were identified to have compound heterozygosity for missense mutations in the NIN gene (Q1222R; N1709S)

PMID: 23665482 -Grosch et al (2013) - in a consanguineous family with a phenotype resembling Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) they identified homozygous missense mutations in the two nearby genes NIN and POLE2 which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. They present evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype.; to: PMID: 22933543 - Dauber et al. (2012) -2 sisters with severe short stature, microcephaly, and developmental delay (Seckel syndrome-7) were identified to have compound heterozygosity for missense mutations in the NIN gene (Q1222R; N1709S)

PMID: 23665482 -Grosch et al (2013) - in a consanguineous family with a phenotype resembling Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) they identified homozygous missense mutations in the two nearby genes NIN and POLE2 which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. They present evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype. The NIN variant is classified as a VUS in OMIM.
Skeletal dysplasia v1.167 IFT81 Eleanor Williams changed review comment from: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

Summary - 2 cases, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype; to: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

PMID: 30080953 - Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). He had narrow thorax, short arms, brachydactyly and short stature. Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.

Summary - 2 cases with SNVs and strong skeletal phenotype, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype. 4th case with tandem duplication of 2 exons.
Skeletal dysplasia v1.167 IFT81 Eleanor Williams commented on gene: IFT81: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

Summary - 2 cases, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype
Skeletal dysplasia v1.167 IFT52 Eleanor Williams Publications for gene: IFT52 were set to 26880018; 27466190
Skeletal dysplasia v1.166 IFT52 Eleanor Williams changed review comment from: Associated with Short-rib thoracic dysplasia 16 with or without polydactyly (#617102) in OMIM.

PMID: 26880018 - Girisha et al. 2016 - 1 case. A child from a consanguineous family who had short stature, narrow thorax, short hands and feet, postaxial polydactyly of hands, pigmentary retinopathy, small teeth and skeletal dysplasia. Whole-exome sequencing revealed a homozygous nonsense variant p.R142* in IFT52. This variant was not found in homozygous state in the 1000Genome project, the Exome Variant Server, the Exome Aggregation Consortium database, CentoMD and exome database of a local NGS service provider. The parents are heterozygous carriers.

PMID: 27466190 - Zhang et al 2016 - 1 case. A non-consanguineous family with two fetuses affected by short-rib polydactyly syndrome (SRPS). Radiographic findings, taken at 20 and 23 weeks of gestation, respectively, were consistent between the two fetuses and showed undermineralized skulls, narrow thoraces with moderately shortened ribs and sharp angulations of some lower thoracic ribs, a flat appearance to the acetabular roofs, reverse campomelia of the humeri, mildly bent femurs, and no polydactyly. In one proband compound heterozygosity for two variants was found - a 1bp deletion leading to a frameshift and premature stop codon and a missense variant (c.878delT, pLeu293AlafsX21 and c.595G > A, p.Ala199Thr). One variant was inherited from each of the parents. The IFT52 mutant cells synthesized a significantly reduced amount of IFT52 protein, leading to reduced synthesis of IFT74, IFT81, IFT88 and ARL13B, other key anterograde complex members. Ciliogenesis was also disrupted in the mutant cells, with a 60% reduction in the presence of cilia on mutant cells and loss of cilia length regulation for the cells with cilia.

PMID: 30242358 - Chen et al. 2018 - 1 case. A child from a consangiuneous family of Hui ethnicity was referred to the clinic with nystagmus and severe visual impairment since infancy also presented with severe growth retardation and mild mental retardation. She had narrow chest with short ribs and micromelic limbs. sandal gap in her right foot and dental dysplasia was also noticed. She was found to have a homozygous variation, IFT52 c.556A>G (p.T186A). This was absent in the two unaffected siblings.

PMID: 31042281 - Dupont et al 2019 - report a family with compound heterogyzous variants (one missense, one causing an inframe mutation that results in less efficient splicing) in IFT52 in two foetuses in which a short rib polydactyly syndrome phenotype is described. One variant is inherited from each of the parents. One fetus also had Tortuous ureters and left pelviectasis. They also report another family in which a fetus with only a renal phenotype and a homozygous variant in IFT52 was identified.; to: Associated with Short-rib thoracic dysplasia 16 with or without polydactyly (#617102) in OMIM.

PMID: 26880018 - Girisha et al. 2016 - 1 case. A child from a consanguineous family who had short stature, narrow thorax, short hands and feet, postaxial polydactyly of hands, pigmentary retinopathy, small teeth and skeletal dysplasia. Whole-exome sequencing revealed a homozygous nonsense variant p.R142* in IFT52. This variant was not found in homozygous state in the 1000Genome project, the Exome Variant Server, the Exome Aggregation Consortium database, CentoMD and exome database of a local NGS service provider. The parents are heterozygous carriers.

PMID: 27466190 - Zhang et al 2016 - 1 case. A non-consanguineous family with two fetuses affected by short-rib polydactyly syndrome (SRPS). Radiographic findings, taken at 20 and 23 weeks of gestation, respectively, were consistent between the two fetuses and showed undermineralized skulls, narrow thoraces with moderately shortened ribs and sharp angulations of some lower thoracic ribs, a flat appearance to the acetabular roofs, reverse campomelia of the humeri, mildly bent femurs, and no polydactyly. In one proband compound heterozygosity for two variants was found - a 1bp deletion leading to a frameshift and premature stop codon and a missense variant (c.878delT, pLeu293AlafsX21 and c.595G > A, p.Ala199Thr). One variant was inherited from each of the parents. The IFT52 mutant cells synthesized a significantly reduced amount of IFT52 protein, leading to reduced synthesis of IFT74, IFT81, IFT88 and ARL13B, other key anterograde complex members. Ciliogenesis was also disrupted in the mutant cells, with a 60% reduction in the presence of cilia on mutant cells and loss of cilia length regulation for the cells with cilia.

PMID: 30242358 - Chen et al. 2018 - 1 case. A child from a consangiuneous family of Hui ethnicity was referred to the clinic with nystagmus and severe visual impairment since infancy also presented with severe growth retardation and mild mental retardation. She had narrow chest with short ribs and micromelic limbs. sandal gap in her right foot and dental dysplasia was also noticed. She was found to have a homozygous variation, IFT52 c.556A>G (p.T186A). This was absent in the two unaffected siblings.

PMID: 31042281 - Dupont et al 2019 - report a family with compound heterogyzous variants (one missense, one causing an inframe mutation that results in less efficient splicing) in IFT52 in two foetuses in which a short rib polydactyly syndrome phenotype is described. One variant is inherited from each of the parents. One fetus also had Tortuous ureters and left pelviectasis. They also report another family in which a fetus with only a renal phenotype and a homozygous variant in IFT52 was identified.

Summary - 3 cases plus a 4th with a milder skeletal phenotype.
Skeletal dysplasia v1.166 IFT52 Eleanor Williams commented on gene: IFT52: Associated with Short-rib thoracic dysplasia 16 with or without polydactyly (#617102) in OMIM.

PMID: 26880018 - Girisha et al. 2016 - 1 case. A child from a consanguineous family who had short stature, narrow thorax, short hands and feet, postaxial polydactyly of hands, pigmentary retinopathy, small teeth and skeletal dysplasia. Whole-exome sequencing revealed a homozygous nonsense variant p.R142* in IFT52. This variant was not found in homozygous state in the 1000Genome project, the Exome Variant Server, the Exome Aggregation Consortium database, CentoMD and exome database of a local NGS service provider. The parents are heterozygous carriers.

PMID: 27466190 - Zhang et al 2016 - 1 case. A non-consanguineous family with two fetuses affected by short-rib polydactyly syndrome (SRPS). Radiographic findings, taken at 20 and 23 weeks of gestation, respectively, were consistent between the two fetuses and showed undermineralized skulls, narrow thoraces with moderately shortened ribs and sharp angulations of some lower thoracic ribs, a flat appearance to the acetabular roofs, reverse campomelia of the humeri, mildly bent femurs, and no polydactyly. In one proband compound heterozygosity for two variants was found - a 1bp deletion leading to a frameshift and premature stop codon and a missense variant (c.878delT, pLeu293AlafsX21 and c.595G > A, p.Ala199Thr). One variant was inherited from each of the parents. The IFT52 mutant cells synthesized a significantly reduced amount of IFT52 protein, leading to reduced synthesis of IFT74, IFT81, IFT88 and ARL13B, other key anterograde complex members. Ciliogenesis was also disrupted in the mutant cells, with a 60% reduction in the presence of cilia on mutant cells and loss of cilia length regulation for the cells with cilia.

PMID: 30242358 - Chen et al. 2018 - 1 case. A child from a consangiuneous family of Hui ethnicity was referred to the clinic with nystagmus and severe visual impairment since infancy also presented with severe growth retardation and mild mental retardation. She had narrow chest with short ribs and micromelic limbs. sandal gap in her right foot and dental dysplasia was also noticed. She was found to have a homozygous variation, IFT52 c.556A>G (p.T186A). This was absent in the two unaffected siblings.

PMID: 31042281 - Dupont et al 2019 - report a family with compound heterogyzous variants (one missense, one causing an inframe mutation that results in less efficient splicing) in IFT52 in two foetuses in which a short rib polydactyly syndrome phenotype is described. One variant is inherited from each of the parents. One fetus also had Tortuous ureters and left pelviectasis. They also report another family in which a fetus with only a renal phenotype and a homozygous variant in IFT52 was identified.
Skeletal dysplasia v1.166 IFT43 Eleanor Williams commented on gene: IFT43: Associated with ?Cranioectodermal dysplasia 3 (#614099) and Short-rib thoracic dysplasia 18 with polydactyly (#617866) in OMIM and with CRANIOECTODERMAL DYSPLASIA TYPE 3 (confirmed) in Gene2Phenotype.

PMID: 21378380- Arts et al. 2011 - 1 case . 2 siblings from a consanguineous family of Moroccan descent with cranioectodermal dysplasia (Sensenbrenner syndrome). The reported phenotype includes Rhizomelic shortening of limbs, narrow thorax, toe syndactyly, brachydactyly, and polydactyly (one sibling). Following genome-wide homozygosity mapping two candidate genes were analyzed and a homozygous missense mutation in the translation initiation codon of the IFT43 gene was identified. Fibroblasts from one of the affected siblings (II:2) show a typical IFT-A defect (ie, accumulation of IFT-B complex proteins in the ciliary tip.

PMID: 28400947 - Duran et al. 2017- 2 cases - in 3 affected individuals from 2 unrelated families with short-rib thoracic dysplasia with polydactyly thye identified homozygosity for missense mutations in the IFT143 gene, M1K and W179R.

PMID: 26892345 - Stokman et al 2016 - 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. They de novo 4.5-Mb microdeletion which contains 65 protein-coding genes, including the ciliary gene IFT43. Immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport.
Skeletal dysplasia v1.166 ICK Eleanor Williams commented on gene: ICK: Mouse model data

PMID: 24853502 - Moon et al 2014 - Ick null mouse embryos displayed cleft palate, hydrocephalus, polydactyly, and delayed skeletal development, closely resembling ECO syndrome phenotypes.

PMID: 24797473 - Chaya et al 2014 - ICK−/− mice died around birth probably because of respiratory failure. ICK−/− mice exhibited preaxial polydactyly in both fore and hind limbs. All four limbs were severely shortened in the ICK−/− mice at E18.5

PMID: 28380258 - Tong et al 2017 - created an Ick R272Q knock-in mouse model that recapitulates ECO pathological phenotypes. Their report focusses on the respiratory phenotype, but they report that mice displayed essential ECO pathological features such as polydactyly and shortened limbs.
Skeletal dysplasia v1.166 ICK Eleanor Williams changed review comment from: PMID: 19185282 - Lahiry et al. (2009) - in 6 affected infants with Endocrine-Cerebroosteodysplasia of Old Order Amish pedigree a homozygous mutation was identified in the ICK gene. The phenotype was severe, involved several organ systems, and resulted in fetal or neonatal death.

PMID: 27069622 Oud et al. (2016) - a Turkish fetus with Endocrine-Cerebroosteodysplasia was found to be homozygous for a missense mutation in the ICK gene that segregated fully with disease in the family and was not found in Turkish controls or public variant databases

PMID: 27466187 Paige Taylor et al (2016) - identified homozygosity for a missense mutation, p.E80K, in Intestinal Cell Kinase, ICK, in one short rib polydactyly syndromes family.; to: PMID: 19185282 - Lahiry et al. (2009) - in 6 affected infants with Endocrine-Cerebroosteodysplasia of Old Order Amish pedigree a homozygous mutation (R272Q) was identified in the ICK gene. The phenotype was severe, involved several organ systems, and resulted in fetal or neonatal death.

PMID: 27069622 Oud et al. (2016) - a Turkish fetus with Endocrine-Cerebroosteodysplasia was found to be homozygous for a missense mutation (G120C) in the ICK gene that segregated fully with disease in the family and was not found in Turkish controls or public variant databases

PMID: 27466187 Paige Taylor et al (2016) - identified homozygosity for a missense mutation, p.E80K, in Intestinal Cell Kinase, ICK, in one short rib polydactyly syndromes family.
Skeletal dysplasia v1.166 GZF1 Eleanor Williams commented on gene: GZF1: Associated with Joint laxity, short stature, and myopia (#617662) in OMIM and with LARSEN SYNDROME (probable) in Gene2Phenotype. Generalized joint laxity is listed as a phenotype for Larsen syndrome in Gene2Phenotype.

PMID: 28475863 - Patel et al 2017 - 2 cases. Family 1 - a multiplex consanguineous Saudi family affected by severe and recurrent large joint dislocation and severe myopia. The index patient also had severe kyphoscoliosis. Both the index patient and her brother had short stature. A homozygous truncating variant in GZF1 was identified (c.865G>T (pGlu289∗). Family 2 - another multiplex consanguineous family affected by severe myopia, retinal detachment, and milder skeletal involvement (generalized joint laxity) A second homozygous truncating GZF1 variant was identified (c.1054dup (p.Thr352Asnfs∗50). Neither variant was present in 2,379 Saudi exomes or the Exome Aggregation Consortium (ExAC) Browser. In functional studies they found using immunofluorescence, strong localization of GZF1 in the developing mouse eye and, to a lesser extent, in the mesenchyme of the developing mouse limb buds. Using 3 patient-derived lymphoblastoid cell lines they found 1,095 genes to be dysregulated in affected individuals.
Skeletal dysplasia v1.166 B9D1 Eleanor Williams commented on gene: B9D1: Associated with ?Meckel syndrome 9 (#614209) and Joubert syndrome 27 (#617120) in OMIM.
Gene2Phenotype reports a probable association with MECKEL SYNDROME 9.

PMID: 24886560 - Romani et al 2014 - report mutations in B9D1 in two patients, a 9-year-old boy (COR363) and a 7-year-old girl (COR346), both presenting with pure JS. The mutations (cG467A; p.R156Q homo, and cA95G; p.Y32C, c.520-522delGTG; p.V175del) were inherited from heterozygous healthy parents, were not reported in public databases, and affected highly conserved residues. Missense mutations were predicted as pathogenic by prediction web tools. Neither patient showed polydactyly or orofacial features although patient COR363's facial dysmorphisms included a triangular face, retrognatism, accentuated philtrum and big ears, and patient COR346's dysmorphic facial features included frontal bossing, macrostomia, thick lips and low-set ears.

PMID: 21493627 - Hopp et al 2011 - In family M456 with Meckel syndrome (MKS), a splice-donor site change in B9D1 was detected in a fetus (c.505+2T>C). Sanger sequencing revealed likely hemizygosity of this variant, with a de novo deletion of the B9D1 locus in the fetus. The deletion spans 1.713 Mb at chromosome 17p11.2, including the complete B9D1 locus. Additionally, 18 other genes were deleted. The authors also identified a novel change in a second MKS gene, CEP290. Sanger sequencing showed that the heterozygous variant, p.R2210C, was inherited from the mother.
Polydactyly, that is typical in MKS, was not noted but the fetus had bilateral club feet and shortened limbs.
Skeletal dysplasia v1.166 IFT81 Eleanor Williams Publications for gene: IFT81 were set to 27666822; 26275418; 28460050
Skeletal dysplasia v1.163 NIPBL Ellen McDonagh Publications for gene: NIPBL were set to
Skeletal dysplasia v1.162 SLC10A7 Eleanor Williams Phenotypes for gene: SLC10A7 were changed from skeletal dysplasia and amelogenesis imperfecta to skeletal dysplasia and amelogenesis imperfecta; Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis 618363
Skeletal dysplasia v1.161 SLC10A7 Eleanor Williams Publications for gene: SLC10A7 were set to 30082715
Skeletal dysplasia v1.160 SLC10A7 Eleanor Williams Classified gene: SLC10A7 as Green List (high evidence)
Skeletal dysplasia v1.160 SLC10A7 Eleanor Williams Added comment: Comment on list classification: Upgrading to green as the are now 6 distinct families with identified variants in SLC10A7 and a relevant phenotype. Evidence also from zebrafish and mouse models.
Skeletal dysplasia v1.160 SLC10A7 Eleanor Williams Gene: slc10a7 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.159 SLC10A7 Eleanor Williams commented on gene: SLC10A7
Skeletal dysplasia v1.159 RASGRP2 Eleanor Williams commented on gene: RASGRP2: PMID: 18709451 - Kilic et al 2009 - 3 families with 4 individuals with Leukocyte adhesion deficiency (LAD) type III
(severe recurrent infections, leukocytosis, and increased bleeding tendency). All patients had increased bone density on
X-ray similar to that seen in patients with osteopetrosis, and variants in the CalDAG-GEF1 gene (now called RASGRP2). A splice junction mutation was found in families 1 and 3. The patient from family 2 had very low levels of CalDAG-GEF1. . Knock out CalDAG-GEFI deficient mice exhibit the same platelet and neutrophil adhesion defect but NO abnormalities in bone density on X-ray.

PMID: 24958846 - Canault et al 2014 - three siblings affected by severe bleeding - whole-exome sequencing identified the culprit mutation (cG742T) in RASGRP2 - couldn't find any mention of a bone density/skeletal dysplasia phenotype.
Skeletal dysplasia v1.159 RAB33B Eleanor Williams commented on gene: RAB33B: Associated with Smith-McCort dysplasia 2 (615222) in OMIM.

PMID: 22652534 - Alshammari et al. (2012) - 1 family - a consanguineous Saudi family segregating Smith-McCort syndrome. Identified a homozygous missense mutation in the RAB33B gene (K46Q). Immunoblot analysis showed severe deficiency of RAB33B in patient cells compared with control cells, and patient fibroblasts also displayed a marked reduction in the immunofluorescence signal corresponding to RAB33B but comparable signal intensity to the Golgi marker giantin.

PMID: 16470731/23042644 - Neumann et al. (2006)/Dupuis et al. (2013) - 1 case. 22-year-old Turkish man with Smith-McCort syndrome-2. Identified a homozygous missense mutation in the RAB33B gene (N148K;). By Western blot analysis and immunofluorescence studies, Dupuis et al. (2013) found marked reduction of the RAB33B protein.

PMID: 28127940 - Salian et al. (2017) - 3 families. 3 SMC patients with four novel pathogenic variants in RAB33B, including homozygosity for c.211C>T (p.R71*), homozygosity for c.365T>C (p.F122S), and compound heterozygosity for c.48delCGGGGCAG (p.G17Vfs*58) and c.490C>T (p.Q164*). The mutations segregated with the disorder in each family.

5 cases in total.
Skeletal dysplasia v1.159 P4HB Eleanor Williams commented on gene: P4HB: Associated with Cole-Carpenter syndrome 1 (112240) in OMIM.

PMID: 25683117 - Rauch et al. (2015) - 2 cases. 2 unrelated male patients with Cole-Carpenter syndrome-1, who exhibited multiple fractures of the long bones as well as craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features/ Identified heterozygosity for the same missense mutation in the P4HB gene ( c.1178A-G transition, Y393C) in both patients. In one the mutation occured de novo, in the other the unaffected father was mosaic for the variant.

PMID: 29384951 - Ouyang and Yang 2017 - 1 case. A 14-month-old Chinese girl presented with prominent ocular proptosis, frontal bossing, craniosynostosis, plump anterior fontanel, growth retardation, osteopenia, and distinctive facial features. Her clinical manifestation is similar to the 2 cases previously described with Cole–Carpenter syndrome-1. Whole-exome sequencing revealed a novel deletion variation in exons 5 to 8 of the P4HB gene, which was found to be heterozygous.

PMID: 30063094 - Porntaveetus et al 2018 - 1 case. First Asian CCS patient possessing the recurrent mutation in P4HB (c.1178A>G ).
Skeletal dysplasia v1.159 MMP13 Eleanor Williams commented on gene: MMP13: PMID: 19615667 - Lausch et al 2009 - found that recessive MAD is caused by homozygous loss of function of either MMP9 or MMP13, whereas dominant MAD is associated with missense mutations in the prodomain of MMP13 that determine autoactivation of MMP13
Skeletal dysplasia v1.159 MMP9 Eleanor Williams commented on gene: MMP9: Associated with Metaphyseal anadysplasia 2 (613073) in OMIM

PMID: 19615667 - Lausch et al 2009 - 1 family. In a recessive kindred, family E, MMP13 was normal, but a c.21T>A transversion in exon 1 altered the start codon of MMP9, substituting methionine with lysine. The variant segregated with the disease in the family.

PMID: 28342220 - Sharony et al 2017 - 1 family. Two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses. NM_004994: c.[559C>T], p.(L187F).

PMID: 24781753 - Li et al 2015 - 0 families. 2 brothers with short stature and mixed epiphyseal and metaphyseal dysplasia. Identified a homozygous C>T transition mutation in exon 2 of MMP13 (c.325C>T, p.(R109*). So not in MMP9.

Only 2 cases reported, 3rd had variant in MMP13 not MMP9.
Skeletal dysplasia v1.159 FZD2 Eleanor Williams commented on gene: FZD2: Associated with Omodysplasia 2 (164745) in OMIM.

PMID: 25759469 - Saal et al 2015 - 1 family. proband with omodysplasia, her unaffected parents and her affected daughter. Identified a de novo mutation (c.1644G>A, p.Trp548*) in FZD2 in the proband and her daughter that was not found in unaffected family members. Show reduced ability of this mutant form of FZD2 to interact with its downstream target DISHEVELLED. Furthermore, expressing the mutant form of FZD2 in vitro is not able to facilitate the cellular response to canonical Wnt signaling like wild-type FZD2.

PMID: 29230162 - Türkmen et al 2017 - 1 patient. A heterozygous de novo mutation (G434V) in the frizzled class receptor 2 (FZD2) gene in a patient with distinct facial features including hypertelorism, bilateral cleft lip/palate, short nose with a broad nasal bridge, microretrognathia, and bilateral shortness of the upper limbs, first metacarpal bones, and middle phalanges of the 5th digits.

PMID: 29383830 - invalid pubmed id

PMID: 29383834 - Nagasaki et al 2018 - 1 patient. 16-year-old boy with OMOD2 or Robinow syndrome-like phenotype. Molecular analysis identified a de novo, heterozygous, nonsense mutation (c.1640C>A, p.S547*) in FZD2.

PMID: 30455931 - Warren et al 2018 - 2 patients. Presented are two patients with autosomal dominant omodysplasia and mutations in the FZD2 gene. The mutations identified have been recently reported, suggesting the possibility of recurrent mutations. The phenotypes of these patients overlap with what has been previously reported, though intellectual disability as seen in our patient is not typical.
Skeletal dysplasia v1.159 MMP13 Eleanor Williams Added comment: Comment on mode of inheritance: Updated mode of inheritance to be in agreement with Tracy Lester's recommendation and OMIM
Skeletal dysplasia v1.159 MMP13 Eleanor Williams Mode of inheritance for gene: MMP13 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.158 FGF23 Eleanor Williams Added comment: Comment on mode of inheritance: Updated mode of inheritance so in agreement with Tracy Lester's recommendation and OMIM
Skeletal dysplasia v1.158 FGF23 Eleanor Williams Mode of inheritance for gene: FGF23 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.157 COL9A3 Eleanor Williams Added comment: Comment on mode of inheritance: Updated in-line with reviewer's recommendations and OMIM
Skeletal dysplasia v1.157 COL9A3 Eleanor Williams Mode of inheritance for gene: COL9A3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.156 CDKN1C Eleanor Williams Added comment: Comment on mode of inheritance: Updating mode of inheritance to reflect expert reviewer's recommendation
Skeletal dysplasia v1.156 CDKN1C Eleanor Williams Mode of inheritance for gene: CDKN1C was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Skeletal dysplasia v1.155 XYLT2 Eleanor Williams commented on gene: XYLT2: PMID: 26027496 - Munns et al 2015 - 3 patients from 2 unrelated families with bone fragility, hearing impairment, cardiac septal defects, and learning difficulties (spondyloocular syndrome). Identified homozygosity for a 1-bp duplication and a 1-bp deletion, respectively. The mutations, which segregated with disease in each family, were not found in public variant databases.

PMID: 26987875- Taylan et al 2016 - report on 4 patients, 2 unrelated patients and 2 siblings, with spondyloocular syndrome and novel mutations in XYLT2.
Skeletal dysplasia v1.155 SERPINH1 Eleanor Williams commented on gene: SERPINH1: PMID: 20188343 - Christiansen et al 2010 - one individual with OI - identified an autosomal-recessive mutation in SERPINH1 (c.233T>C, p.Leu78Pro).

PMID: 25510505 - Duran et al 2015 - two affected siblings with a moderately severe form of OI. Homozygosity for a single nucleotide variant in SERPINH1 (c.710T>C, p.237Met>Thr) was identified. The parents were carriers of the sequence change.

Also Dachshund (dog) model of OI:
PMID: 19629171 - Drögemüller et al 2009 - investigated Dachshunds with an autosomal recessive form of OI. A missense mutation (c.977C>T, p.L326P) located in an evolutionary conserved domain was perfectly associated with the OI phenotype. 11 affected dogs were homozygous C/C and all 13 known carriers were heterozygous C/T. Affected dogs iikely bred from a founder individual.
Skeletal dysplasia v1.155 HDAC4 Eleanor Williams commented on gene: HDAC4: Not associated with a phenotype in OMIM.
See review of this gene on Limb disorders panel - https://panelapp.genomicsengland.co.uk/panels/384/gene/HDAC4/
Conclusion was haploinsufficiency of HDAC4 appears to be associated with Brachydactyly type E but not always intellectual disability.
Skeletal dysplasia v1.155 PGM3 Eleanor Williams commented on gene: PGM3: PMID: 24931394 Stray-Pedersen et al 2014 - identified three unrelated children with recurrent infections, congenital leukopenia including neutropenia, B and T cell lymphopenia, and progression to bone marrow failure. Whole-exome sequencing demonstrated deleterious mutations in PGM3 in all three subjects, Two of the three children had skeletal anomalies resembling Desbuquois dysplasia: short stature, brachydactyly, dysmorphic facial features, and intellectual disability. However, these additional features were absent in the third child, showing the clinical variability of the disease.

PMID: 28543917 - Pacheco-Cuéllar et al 2017 - identified a novel homozygous mutation (c.1135T>C; p.Phe379Leu) in PGM3 in two siblings with bone marrow failure, severe combined immunodeficiency, renal and intestinal malformations, and a skeletal dysplasia resembling Desbuquois dysplasia
Skeletal dysplasia v1.155 WDR19 Eleanor Williams commented on gene: WDR19: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient with Jeune syndrome and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .
Skeletal dysplasia v1.155 RBPJ Eleanor Williams commented on gene: RBPJ: PMID: 22883147 - Hassed et al. [2012] identified mutations in RBPJ through exome sequencing in two independent kindreds with autosomal dominant AOS.

PMID: 28160419 - Hassad et al 2017 - don't think they report any new families.
Skeletal dysplasia v1.155 NIN Eleanor Williams commented on gene: NIN: PMID: 22933543 - Dauber et al. (2012) -2 sisters with severe short stature, microcephaly, and developmental delay (Seckel syndrome-7) were identified to have compound heterozygosity for missense mutations in the NIN gene (Q1222R; N1709S)

PMID: 23665482 -Grosch et al (2013) - in a consanguineous family with a phenotype resembling Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) they identified homozygous missense mutations in the two nearby genes NIN and POLE2 which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. They present evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype.
Skeletal dysplasia v1.155 IFT81 Eleanor Williams commented on gene: IFT81: Additional publication - PMID: 30080953 Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.
Skeletal dysplasia v1.155 IFT52 Eleanor Williams Publications for gene: IFT52 were set to 2688018; 27466190
Skeletal dysplasia v1.154 ICK Eleanor Williams commented on gene: ICK: PMID: 19185282 - Lahiry et al. (2009) - in 6 affected infants with Endocrine-Cerebroosteodysplasia of Old Order Amish pedigree a homozygous mutation was identified in the ICK gene. The phenotype was severe, involved several organ systems, and resulted in fetal or neonatal death.

PMID: 27069622 Oud et al. (2016) - a Turkish fetus with Endocrine-Cerebroosteodysplasia was found to be homozygous for a missense mutation in the ICK gene that segregated fully with disease in the family and was not found in Turkish controls or public variant databases

PMID: 27466187 Paige Taylor et al (2016) - identified homozygosity for a missense mutation, p.E80K, in Intestinal Cell Kinase, ICK, in one short rib polydactyly syndromes family.
Skeletal dysplasia v1.154 GPX4 Eleanor Williams commented on gene: GPX4: PMID: 24706940 - Smith et al 2014 - 2 cases. Case 1 - child with Sedaghatian-type spondylometaphyseal dysplasia (SSMD) heterozygous for two rare variants in GPX4;(c.587+5G>A) was inherited from the mother, and the second (c.588-8_588-4del) was de novo; both were predicted to impact splicing of GPX4. Case 2 - DNA from the child with SSMD was not available, the two unaffected parents were found by Sanger sequencing to each carry the same heterozygous stop mutation in exon 3 of GPX4, c.381C>A, p.Tyr127*.

So 3 variants but from 2 cases. PubMed search did not find any other cases.
Skeletal dysplasia v1.154 IDH2 Eleanor Williams commented on gene: IDH2: PMID: 20847235 - Kranendijk et al. (2010) - 15 of 17 cases of D-2-hydroxyglutaric aciduria without mutation in the D2HGDH gene a heterozygous mutation was found in the IDH2 gene. 14 had an arg140-to-gln mutation (R140Q) and 1 had an arg140-to-gly mutation (R140G).

PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo.
Skeletal dysplasia v1.154 RAD21 Eleanor Williams Publications for gene: RAD21 were set to
Skeletal dysplasia v1.153 RAD21 Eleanor Williams commented on gene: RAD21: OMIM: - 2 cases reported in OMIM (PMID: 22633399, Deardorff et al 2012) plus 3 patients with overlapping deletions covering RAD21 (aswell as other genes).

Other publications with patients with Cornelia de Lange and RAD21 variants
PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype
PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance.
PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance
PMID: 27620904 - Martinez et al., 2017 - 1 patient
Skeletal dysplasia v1.153 PAM16 Eleanor Williams commented on gene: PAM16: PMID: 27354339 - Moosa et al 2016 - 1 patient with a spondylometaphyseal dysplasia, most closely resembling odontochondrodysplasi. A homozygous c.221A>C (p.Q74P) mutation in PAM16, which was not present in the ExAC database was identified.

PMID: 24786642 - Mehawej et al 2014 - Two unrelated consanguineous Lebanese families with four affected cases presenting a novel type of early lethal spondylodysplastic dysplasia. Identified c.226A>G transition in MAGMAS (PAM16) to segregated with the disease in both families. The mutation was homozygous in the patients, heterozygous in the parents and in the unaffected sibs in both families. Likely founder mutation.
Show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein.
Skeletal dysplasia v1.153 HOXD11 Eleanor Williams Publications for gene HOXD11 were changed from to Fleischman 2013 Blood 122:4837 http://www.bloodjournal.org/content/122/21/4837 (not in PubMed)
Skeletal dysplasia v1.153 FIG4 Eleanor Williams Added phenotypes Yunis-Varon syndrome 216340 for gene: FIG4
Skeletal dysplasia v1.153 EIF2AK3 Eleanor Williams Added phenotypes Wolcott-Rallison syndrome 226980 for gene: EIF2AK3
Skeletal dysplasia v1.153 WRN Eleanor Williams Added phenotypes Werner syndrome -277700 for gene: WRN
Skeletal dysplasia v1.153 ADAMTS17 Eleanor Williams Added phenotypes Weill-Marchesani syndrome type 4 for gene: ADAMTS17
Skeletal dysplasia v1.153 ADAMTS10 Eleanor Williams Added phenotypes Weill-Marchesani syndrome type 1 for gene: ADAMTS10
Skeletal dysplasia v1.153 LTBP2 Eleanor Williams Added phenotypes Weill-Marchesani for gene: LTBP2
Publications for gene LTBP2 were changed from to 22539340
Skeletal dysplasia v1.153 EZH2 Eleanor Williams Added phenotypes Weaver syndrome for gene: EZH2
Skeletal dysplasia v1.153 CYP27B1 Eleanor Williams Added phenotypes Vitamin D-dependent rickets, type I 264700 for gene: CYP27B1
Skeletal dysplasia v1.153 PUF60 Eleanor Williams Added phenotypes Verheij syndrome, 615583; VRJS for gene: PUF60
Publications for gene PUF60 were changed from 28327570; 27804958; 24140112 to 27804958; 28327570; 24140112
Skeletal dysplasia v1.153 SCARF2 Eleanor Williams Added phenotypes Van den Ende-Gupta syndrome 600920 for gene: SCARF2
Skeletal dysplasia v1.153 TP63 Eleanor Williams Added phenotypes Rapp-Hodgkin syndrome 129400; Orofacial cleft 8 129400; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 604292; Hay-Wells syndrome 106260; ULT syndrome 103285; Split-hand/foot malformation 4 605289; Limb-mammary syndrome 603543 for gene: TP63
Skeletal dysplasia v1.153 TBX3 Eleanor Williams Added phenotypes Ulnar-mammary syndrome 181450 for gene: TBX3
Publications for gene TBX3 were changed from to 28961683; 30654152; 28145909
Skeletal dysplasia v1.153 GALNT3 Eleanor Williams Added phenotypes Tumoral calcinosis, hyperphosphatemic, familial I 211900 for gene: GALNT3
Skeletal dysplasia v1.153 TRPS1 Eleanor Williams Added phenotypes Trichorhinophalangeal syndrome, type III 190351; Trichorhinophalangeal syndrome, type I 190350 for gene: TRPS1
Skeletal dysplasia v1.153 POLR1C Eleanor Williams Added phenotypes Treacher Collins syndrome 3 248390 for gene: POLR1C
Skeletal dysplasia v1.153 POLR1D Eleanor Williams Added phenotypes Treacher Collins syndrome 2 613717 for gene: POLR1D
Skeletal dysplasia v1.153 TCOF1 Eleanor Williams Added phenotypes Treacher Collins syndrome 1 154500 for gene: TCOF1
Skeletal dysplasia v1.153 TALDO1 Eleanor Williams Added phenotypes Transaldolase deficiency 606003 for gene: TALDO1
Publications for gene TALDO1 were changed from 25388407; 26238251 to 26238251; 25388407
Skeletal dysplasia v1.153 SALL1 Eleanor Williams Added phenotypes Townes Brocks syndrome (Renal-Ear-Anal-Radial syndrome) 107480 for gene: SALL1
Skeletal dysplasia v1.153 RBM8A Eleanor Williams Added phenotypes Thrombocytopenia-absent radius syndrome 274000 for gene: RBM8A
Skeletal dysplasia v1.153 THPO Eleanor Williams Added phenotypes Thrombocythemia 1 187950 (rare presentation with congenital limb defects) for gene: THPO
Publications for gene THPO were changed from 22453305; 19553636 to 19553636; 22453305
Skeletal dysplasia v1.153 WNT3 Eleanor Williams Added phenotypes Tetra-amelia syndrome 273395 for gene: WNT3
Publications for gene WNT3 were changed from to 14872406
Skeletal dysplasia v1.153 CHSY1 Eleanor Williams Added phenotypes Temtamy preaxial brachydactyly syndrome 605282 for gene: CHSY1
Skeletal dysplasia v1.153 DNMT3A Eleanor Williams Added phenotypes Tatton-Brown-Rahman syndrome 615879 for gene: DNMT3A
Skeletal dysplasia v1.153 FBLN1 Eleanor Williams Added phenotypes Synpolydactyly, 3/3'4, associated with metacarpal and metatarsal synostoses 608180 for gene: FBLN1
Publications for gene FBLN1 were changed from to 24084572
Skeletal dysplasia v1.153 BHLHA9 Eleanor Williams Added phenotypes Syndactyly, mesoaxial synostotic, with phalangeal reduction 609432 for gene: BHLHA9
Skeletal dysplasia v1.153 CKAP2L Eleanor Williams Added phenotypes Syndactyly with microcephaly and MR (Filippi syndrome) 272440 for gene: CKAP2L
Skeletal dysplasia v1.153 LIFR Eleanor Williams Added phenotypes Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome 601559 for gene: LIFR
Skeletal dysplasia v1.153 COL9A2 Eleanor Williams Added phenotypes Epiphyseal dysplasia, multiple, 2 600204; Stickler syndrome, type V 614284; Stickler syndrome, type V, 614284; {Intervertebral disc disease, susceptibility to}, 603932 for gene: COL9A2
Skeletal dysplasia v1.153 FAM58A Eleanor Williams Added phenotypes STAR syndrome 300707 for gene: FAM58A
Skeletal dysplasia v1.153 TTC21B Eleanor Williams Added phenotypes Nephronophthisis 12, 613820; Asphyxiating Thoracic Dystrophy; SRTD4 for gene: TTC21B
Skeletal dysplasia v1.153 IFT172 Eleanor Williams Added phenotypes Short-rib thoracic dysplasia 10 with or without polydactyly, 615630; SRTD10 for gene: IFT172
Skeletal dysplasia v1.153 XYLT2 Eleanor Williams Added phenotypes Spondyloocular syndrome 605822 for gene: XYLT2
Skeletal dysplasia v1.153 GPX4 Eleanor Williams Added phenotypes Spondylometaphyseal dysplasia, Sedaghatian type 250220 for gene: GPX4
Publications for gene GPX4 were changed from to 24706940
Skeletal dysplasia v1.153 PAM16 Eleanor Williams Added phenotypes Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type 613320 for gene: PAM16
Publications for gene PAM16 were changed from 27354339; 24786642 to 24786642; 27354339
Skeletal dysplasia v1.153 FN1 Eleanor Williams Added phenotypes Spondylometaphyseal dysplasia, corner fracture type 184255 for gene: FN1
Publications for gene FN1 were changed from to 29100092
Skeletal dysplasia v1.153 C21orf2 Eleanor Williams Added phenotypes Spondylometaphyseal dysplasia, axial 602271 for gene: C21orf2
Skeletal dysplasia v1.153 PCYT1A Eleanor Williams Added phenotypes Spondylometaphyseal dysplasia with cone-rod dystrophy 608940 for gene: PCYT1A
Skeletal dysplasia v1.153 DDR2 Eleanor Williams Added phenotypes Spondylometaepiphyseal dysplasia, short limb-hand type 271665, at least 3 cases reported for gene: DDR2
Skeletal dysplasia v1.153 CHST3 Eleanor Williams Added phenotypes Spondyloepiphyseal dysplasia with congenital joint dislocations (recessive Larsen syndrome) 143095 for gene: CHST3
Skeletal dysplasia v1.153 TRAPPC2 Eleanor Williams Added phenotypes Spondyloepiphyseal dysplasia tarda 313400 for gene: TRAPPC2
Skeletal dysplasia v1.153 NANS Eleanor Williams Added phenotypes Spondyloepimetaphyseal dysplasia, Camera-Genevieve type 610442 for gene: NANS
Skeletal dysplasia v1.153 KIF22 Eleanor Williams Added phenotypes Spondyloepimetaphyseal dysplasia with joint laxity, type 2 603546 for gene: KIF22
Skeletal dysplasia v1.153 ACP5 Eleanor Williams Added phenotypes Spondyloenchondrodysplasia with immune dysregulation 607944 for gene: ACP5
Skeletal dysplasia v1.153 RIPPLY2 Eleanor Williams Added phenotypes Spondylocostal dysostosis 6 - 616566 for gene: RIPPLY2
Publications for gene RIPPLY2 were changed from to 26238661; 25343988
Skeletal dysplasia v1.153 TBX6 Eleanor Williams Added phenotypes Spondylocostal dysostosis 5 122600 for gene: TBX6
Skeletal dysplasia v1.153 HES7 Eleanor Williams Added phenotypes Spondylocostal dysostosis 4, autosomal recessive 613686 for gene: HES7
Skeletal dysplasia v1.153 LFNG Eleanor Williams Added phenotypes Spondylocostal dysostosis 3, autosomal recessive 609813 for gene: LFNG
Publications for gene LFNG were changed from to 30196550; 16385447
Skeletal dysplasia v1.153 MESP2 Eleanor Williams Added phenotypes Spondylocostal dysostosis 2, autosomal recessive 608681 for gene: MESP2
Publications for gene MESP2 were changed from to 15122512; 18485326
Skeletal dysplasia v1.153 DLL3 Eleanor Williams Added phenotypes Spondylocostal dysostosis 1, autosomal recessive 277300 for gene: DLL3
Skeletal dysplasia v1.153 SLC39A13 Eleanor Williams Added phenotypes Spondylocheirodysplasia, Ehlers-Danlos syndrome-like 612350 for gene: SLC39A13
Skeletal dysplasia v1.153 NKX3-2 Eleanor Williams Added phenotypes Spondylo-megaepiphyseal-metaphyseal dysplasia 613330 for gene: NKX3-2
Skeletal dysplasia v1.153 WNT10B Eleanor Williams Added phenotypes Split-hand/foot malformation 6 225300 for gene: WNT10B
Skeletal dysplasia v1.153 DLX5 Eleanor Williams Added phenotypes Split-hand/foot malformation 1 with sensorineural hearing loss 220600 for gene: DLX5
Publications for gene DLX5 were changed from to 27085093
Skeletal dysplasia v1.153 DLX6 Eleanor Williams Added phenotypes Split-hand/foot malformation 1 183600 for gene: DLX6
Publications for gene DLX6 were changed from to 28611547
Skeletal dysplasia v1.153 NSD1 Eleanor Williams Added phenotypes Sotos syndrome 1 117550 for gene: NSD1
Skeletal dysplasia v1.153 RAB33B Eleanor Williams Added phenotypes Smith-McCort dysplasia 2 615222 for gene: RAB33B
Skeletal dysplasia v1.153 IFIH1 Eleanor Williams Added phenotypes Singleton-Merten syndrome 1 (182250) for gene: IFIH1
Publications for gene IFIH1 were changed from to 25620204
Skeletal dysplasia v1.153 NEU1 Eleanor Williams Added phenotypes Sialidosis, type II 256550; Sialidosis, type I 256550 for gene: NEU1
Skeletal dysplasia v1.153 SLC17A5 Eleanor Williams Added phenotypes Sialic acid storage disorder, infantile 269920 for gene: SLC17A5
Skeletal dysplasia v1.153 SBDS Eleanor Williams Added phenotypes Shwachman-Diamond syndrome 260400 for gene: SBDS
Skeletal dysplasia v1.153 SKI Eleanor Williams Added phenotypes Shprintzen-Goldberg syndrome 182212 for gene: SKI
Skeletal dysplasia v1.153 IFT140 Eleanor Williams Added phenotypes Short-rib thoracic dysplasia 9 with of without polydactyly, 266920 for gene: IFT140
Skeletal dysplasia v1.153 WDR60 Eleanor Williams Added phenotypes Short-rib thoracic dysplasia 8 with or without polydactyly 615503 for gene: WDR60
Skeletal dysplasia v1.153 WDR19 Eleanor Williams Added phenotypes Cranioectodermal dysplasia 4, 614378; Short-rib thoracic dysplasia 5 with or without polydactyly, 614376 for gene: WDR19
Publications for gene WDR19 were changed from to 22019273; 24504730
Skeletal dysplasia v1.153 IFT80 Eleanor Williams Added phenotypes Short-rib thoracic dysplasia 2 with or without polydactyly 611263 for gene: IFT80
Skeletal dysplasia v1.153 IFT43 Eleanor Williams Added phenotypes Short-rib thoracic dysplasia 18 with polydactyly - 617866; ?Cranioectodermal dysplasia 3 - 614099 for gene: IFT43
Publications for gene IFT43 were changed from 21378380; 22791528; 26892345; 24027799 to 26892345; 24027799; 28400947; 22791528; 21378380
Skeletal dysplasia v1.153 TCTEX1D2 Eleanor Williams Added phenotypes Short-rib thoracic dysplasia 17 with or without polydactyly, 617405 for gene: TCTEX1D2
Publications for gene TCTEX1D2 were changed from 26044572; 25830415 to 26044572; 25830415
Skeletal dysplasia v1.153 IFT52 Eleanor Williams Added phenotypes SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY, SRTD16 #617102 for gene: IFT52
Publications for gene IFT52 were changed from 27466190; 26880018 to 2688018; 27466190
Skeletal dysplasia v1.153 DYNC2LI1 Eleanor Williams Added phenotypes SHORT-RIB THORACIC DYSPLASIA 15 WITH POLYDACTYLY; SRTD15 #617088 for gene: DYNC2LI1
Skeletal dysplasia v1.153 CEP120 Eleanor Williams Added phenotypes Joubert syndrome 213300; Short-rib thoracic dysplasia 13 with or without polydactyly 616300 for gene: CEP120
Publications for gene CEP120 were changed from 27208211; 27208211 to 27208211
Skeletal dysplasia v1.153 WDR34 Eleanor Williams Added phenotypes Short-rib thoracic dysplasia 11 with or without polydactyly, 615633 for gene: WDR34
Skeletal dysplasia v1.153 PIK3R1 Eleanor Williams Added phenotypes SHORT syndrome 269880 for gene: PIK3R1
Skeletal dysplasia v1.153 POC1A Eleanor Williams Added phenotypes Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis 614813 for gene: POC1A
Publications for gene POC1A were changed from 26162852; 26336158; 26374189 to 26374189; 26162852; 26336158
Skeletal dysplasia v1.153 XRCC4 Eleanor Williams Added phenotypes Short stature, microcephaly, and endocrine dysfunction 616541 for gene: XRCC4
Skeletal dysplasia v1.153 PRMT7 Eleanor Williams Added phenotypes Short stature, brachydactyly, intellectual developmental disability, and seizures 617157 for gene: PRMT7
Skeletal dysplasia v1.153 NEK1 Eleanor Williams Added phenotypes Short rib thoracic dysplasia 6 with or without polydactyly - 263520 for gene: NEK1
Skeletal dysplasia v1.153 DYNC2H1 Eleanor Williams Added phenotypes Short rib polydactyly syndrome (SRPS) type 3 with or without polydactyly, 613091 for gene: DYNC2H1
Publications for gene DYNC2H1 were changed from to 21211617
Skeletal dysplasia v1.153 ASXL2 Eleanor Williams Added phenotypes Shashi-Pena syndrome 617190 for gene: ASXL2
Skeletal dysplasia v1.153 NIN Eleanor Williams Added phenotypes Seckel syndrome 7 614851 for gene: NIN
Publications for gene NIN were changed from 23665482; 22933543 to 22933543; 23665482
Skeletal dysplasia v1.153 SLC35D1 Eleanor Williams Added phenotypes Schneckenbecken dysplasia 269250 for gene: SLC35D1
Skeletal dysplasia v1.153 SMARCAL1 Eleanor Williams Added phenotypes Schimke immunoosseous dysplasia 242900 for gene: SMARCAL1
Skeletal dysplasia v1.153 EP300 Eleanor Williams Added phenotypes Rubinstein-Taybi syndrome 180849 for gene: EP300
Skeletal dysplasia v1.153 CREBBP Eleanor Williams Added phenotypes Rubinstein-Taybi syndrome 180849 for gene: CREBBP
Skeletal dysplasia v1.153 DVL3 Eleanor Williams Added phenotypes Robinow syndrome, autosomal dominant 3, 616894 for gene: DVL3
Skeletal dysplasia v1.153 DVL1 Eleanor Williams Added phenotypes Robinow syndrome, autosomal dominant 2 616331 for gene: DVL1
Publications for gene DVL1 were changed from to 25817016; 25817014
Skeletal dysplasia v1.153 WNT5A Eleanor Williams Added phenotypes Robinow syndrome, autosomal dominant 1 180700 for gene: WNT5A
Skeletal dysplasia v1.153 ESCO2 Eleanor Williams Added phenotypes SC phocomelia syndrome 269000; Roberts syndrome 268300 for gene: ESCO2
Skeletal dysplasia v1.153 PEX7 Eleanor Williams Added phenotypes Rhizomelic chondrodysplasia punctata, type 1, 215100; Rhizomelic CDP type 1 for gene: PEX7
Publications for gene PEX7 were changed from to 28742517; 25800479; 7719337
Skeletal dysplasia v1.153 GNPAT Eleanor Williams Added phenotypes Rhizomelic Chondrodysplasia Punctata; RCDP2; Rhizomelic chondrodysplasia punctata type 2; Chondrodysplasia punctata, rhizomelic, type 2, 222765 for gene: GNPAT
Skeletal dysplasia v1.153 FAM20C Eleanor Williams Added phenotypes Raine syndrome 259775 for gene: FAM20C
Skeletal dysplasia v1.153 HOXA11 Eleanor Williams Added phenotypes Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 605432 for gene: HOXA11
Publications for gene HOXA11 were changed from to 11101832
Skeletal dysplasia v1.153 SFRP4 Eleanor Williams Added phenotypes PYL; Metaphyseal dysplasia; Pyle disease 265900 for gene: SFRP4
Publications for gene SFRP4 were changed from 27355534; 28100910; 27117872; 24096177; 26273529; 22965941; 22387305; 20174869; 27117872 to 27355534; 26273529; 20174869; 27117872; 22965941; 28100910; 24096177; 22387305
Skeletal dysplasia v1.153 CTSK Eleanor Williams Added phenotypes Pycnodysostosis 265800 for gene: CTSK
Skeletal dysplasia v1.153 PSPH Eleanor Williams Added phenotypes Phosphoserine phosphatase deficiency 614023 for gene: PSPH
Skeletal dysplasia v1.153 PEX5 Eleanor Williams Added phenotypes Peroxisome biogenesis disorder 2A (Zellweger) 214110; Rhizomelic chondrodysplasia punctata, type 5 616716 for gene: PEX5
Skeletal dysplasia v1.153 DIS3L2 Eleanor Williams Added phenotypes Perlman syndrome 267000 for gene: DIS3L2
Publications for gene DIS3L2 were changed from to 22306653
Skeletal dysplasia v1.153 TNFRSF11B Eleanor Williams Added phenotypes Paget disease of bone 5, juvenile-onset 239000 for gene: TNFRSF11B
Skeletal dysplasia v1.153 SNX10 Eleanor Williams Added phenotypes Osteopetrosis, autosomal recessive 8 615085 for gene: SNX10
Skeletal dysplasia v1.153 PLEKHM1 Eleanor Williams Added phenotypes Osteopetrosis, autosomal recessive 6 - 611497; Osteopetrosis, autosomal dominant 3 - 618107 for gene: PLEKHM1
Publications for gene PLEKHM1 were changed from 17997709 to 17404618; 27291868; 17997709
Skeletal dysplasia v1.153 OSTM1 Eleanor Williams Added phenotypes Osteopetrosis, autosomal recessive 5 259720 for gene: OSTM1
Skeletal dysplasia v1.153 CA2 Eleanor Williams Added phenotypes Osteopetrosis, autosomal recessive 3, with renal tubular acidosis 259730 for gene: CA2
Skeletal dysplasia v1.153 TNFSF11 Eleanor Williams Added phenotypes Osteopetrosis, autosomal recessive 2 259710 for gene: TNFSF11
Skeletal dysplasia v1.153 TCIRG1 Eleanor Williams Added phenotypes Osteopetrosis, autosomal recessive 1 259700 for gene: TCIRG1
Skeletal dysplasia v1.153 CLCN7 Eleanor Williams Added phenotypes Osteopetrosis, autosomal recessive 4 611490; Osteopetrosis, autosomal dominant 2 166600 for gene: CLCN7
Skeletal dysplasia v1.153 AMER1 Eleanor Williams Added phenotypes Osteopathia striata with cranial sclerosis 300373 for gene: AMER1
Skeletal dysplasia v1.153 TNFRSF11A Eleanor Williams Added phenotypes Osteolysis, familial expansile 174810; Osteopetrosis, autosomal recessive 7 612301; Paget disease of bone 2, early-onset 602080 for gene: TNFRSF11A
Skeletal dysplasia v1.153 CREB3L1 Eleanor Williams Added phenotypes Osteogenesis imperfecta, type XVI 616229 for gene: CREB3L1
Publications for gene CREB3L1 were changed from 25007323 to 25007323; 29936144.; 28817112
Skeletal dysplasia v1.153 BMP1 Eleanor Williams Added phenotypes Osteogenesis imperfecta, type XIII, 614856 for gene: BMP1
Skeletal dysplasia v1.153 SP7 Eleanor Williams Added phenotypes Osteogenesis imperfecta, type XII 613849 for gene: SP7
Publications for gene SP7 were changed from 20579626 to 2057926; 29382611
Skeletal dysplasia v1.153 P3H1 Eleanor Williams Added phenotypes Osteogenesis imperfecta, type VIII 610915 for gene: P3H1
Skeletal dysplasia v1.153 CRTAP Eleanor Williams Added phenotypes Osteogenesis imperfecta, type VII 610682 for gene: CRTAP
Skeletal dysplasia v1.153 IFITM5 Eleanor Williams Added phenotypes Osteogenesis imperfecta, type V 610967 for gene: IFITM5
Skeletal dysplasia v1.153 PPIB Eleanor Williams Added phenotypes Osteogenesis imperfecta, type IX 259440 for gene: PPIB
Skeletal dysplasia v1.153 ACAN Eleanor Williams Added phenotypes Osteochondritis dissecans, short stature, and early-onset osteoarthritis 165800; Spondyloepimetaphyseal dysplasia, aggrecan type 61283; Spondyloepiphyseal dysplasia, Kimberley type 608361 for gene: ACAN
Skeletal dysplasia v1.153 C2CD3 Eleanor Williams Added phenotypes Orofaciodigital syndrome XIV 615948 for gene: C2CD3
Skeletal dysplasia v1.153 INPPL1 Eleanor Williams Added phenotypes Opsismodysplasia 258480 for gene: INPPL1
Skeletal dysplasia v1.153 SMOC1 Eleanor Williams Added phenotypes Microphthalmia with limb anomalies 206920; Ophthalmo-acromelic syndrome; Polydactyly for gene: SMOC1
Skeletal dysplasia v1.153 GPC6 Eleanor Williams Added phenotypes Omodysplasia 1 258315 for gene: GPC6
Skeletal dysplasia v1.153 SALL4 Eleanor Williams Added phenotypes Okihiro (Duane-radial ray) syndrome 607323; IVIC syndrome 147750 for gene: SALL4
Skeletal dysplasia v1.153 SERPINH1 Eleanor Williams Added phenotypes Osteogenesis Imperfecta, Recessive; OI3; Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias; {Preterm premature rupture of the membranes, susceptibility to}, 610504; Osteogenesis imperfecta, type X, 613848 for gene: SERPINH1
Publications for gene SERPINH1 were changed from to 25510505; 20188343
Skeletal dysplasia v1.153 WNT1 Eleanor Williams Added phenotypes osteogenesis imperfecta; OI/osteoporosis; {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, 615221; Osteogenesis imperfecta, type XV, 615220 for gene: WNT1
Skeletal dysplasia v1.153 SERPINF1 Eleanor Williams Added phenotypes Osteogenesis imperfecta, type VI, 613982; osteogenesis imperfecta; OI/osteoporosis; Osteogenesis Imperfecta, Recessive for gene: SERPINF1
Skeletal dysplasia v1.153 NF1 Eleanor Williams Added phenotypes Neurofibromatosis, familial spinal 162210; Neurofibromatosis-Noonan syndrome 601321; Neurofibromatosis, type 1 162200 for gene: NF1
Skeletal dysplasia v1.153 PSAT1 Eleanor Williams Added phenotypes Neu-Laxova syndrome 2 616038 for gene: PSAT1
Skeletal dysplasia v1.153 PHGDH Eleanor Williams Added phenotypes Neu-Laxova syndrome 1 256520; Phosphoglycerate dehydrogenase deficiency 601815 for gene: PHGDH
Skeletal dysplasia v1.153 TYROBP Eleanor Williams Added phenotypes Nasu-Hakola disease 221770 for gene: TYROBP
Skeletal dysplasia v1.153 TREM2 Eleanor Williams Added phenotypes Nasu-Hakola disease 221770 for gene: TREM2
Skeletal dysplasia v1.153 LMX1B Eleanor Williams Added phenotypes Nail-patella syndrome 161200 for gene: LMX1B
Skeletal dysplasia v1.153 SMAD4 Eleanor Williams Added phenotypes Myhre syndrome 139210 for gene: SMAD4
Skeletal dysplasia v1.153 SUMF1 Eleanor Williams Added phenotypes Multiple sulfatase deficiency 272200 for gene: SUMF1
Skeletal dysplasia v1.153 PIGT Eleanor Williams Added phenotypes Multiple congenital anomalies-hypotonia-seizures syndrome 3 615398 for gene: PIGT
Publications for gene PIGT were changed from 28327575 to 29868109; 28327575
Skeletal dysplasia v1.153 MMP2 Eleanor Williams Added phenotypes Multicentric osteolysis, nodulosis, and arthropathy 259600 for gene: MMP2
Skeletal dysplasia v1.153 MAFB Eleanor Williams Added phenotypes Multicentric carpotarsal osteolysis syndrome 166300 for gene: MAFB
Publications for gene MAFB were changed from to 2387013; 30305815; 30430035
Skeletal dysplasia v1.153 GUSB Eleanor Williams Added phenotypes Mucopolysaccharidosis VII 253220 for gene: GUSB
Skeletal dysplasia v1.153 ARSB Eleanor Williams Added phenotypes Mucopolysaccharidosis type VI (Maroteaux-Lamy) 253200 for gene: ARSB
Skeletal dysplasia v1.153 GNS Eleanor Williams Added phenotypes Mucopolysaccharidosis type IIID 252940 for gene: GNS
Skeletal dysplasia v1.153 HGSNAT Eleanor Williams Added phenotypes Mucopolysaccharidosis type IIIC (Sanfilippo C) 252930 for gene: HGSNAT
Skeletal dysplasia v1.153 NAGLU Eleanor Williams Added phenotypes Mucopolysaccharidosis type IIIB (Sanfilippo B) 252920 for gene: NAGLU
Skeletal dysplasia v1.153 GALNS Eleanor Williams Added phenotypes Mucopolysaccharidosis IVA 253000 for gene: GALNS
Skeletal dysplasia v1.153 IDS Eleanor Williams Added phenotypes Mucopolysaccharidosis II 309900 for gene: IDS
Skeletal dysplasia v1.153 IDUA Eleanor Williams Added phenotypes Mucopolysaccharidosis Ih 607014; Mucopolysaccharidosis Is 607016; Mucopolysaccharidosis Ih/s 607015 for gene: IDUA
Skeletal dysplasia v1.153 SGSH Eleanor Williams Added phenotypes Mucopolysaccharidisis type IIIA (Sanfilippo A) 252900 for gene: SGSH
Skeletal dysplasia v1.153 GNPTG Eleanor Williams Added phenotypes Mucolipidosis III gamma 252605 for gene: GNPTG
Skeletal dysplasia v1.153 GNPTAB Eleanor Williams Added phenotypes Mucolipidosis III alpha/beta 252600; Mucolipidosis II alpha/beta 252500 for gene: GNPTAB
Skeletal dysplasia v1.153 DHODH Eleanor Williams Added phenotypes Miller syndrome (postaxial acrofacial dysostosis) 263750 for gene: DHODH
Skeletal dysplasia v1.153 PCNT Eleanor Williams Added phenotypes Microcephalic osteodysplastic primordial dwarfism, type II 210720 for gene: PCNT
Skeletal dysplasia v1.153 RNU4ATAC Eleanor Williams Added phenotypes Roifman syndrome 616651; Microcephalic osteodysplastic primordial dwarfism, type I 210710 for gene: RNU4ATAC
Skeletal dysplasia v1.153 IDH1 Eleanor Williams Added phenotypes Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria 614875; Maffucci syndrome 614569; Ollier disease/ Dyschondroplasia 166000 for gene: IDH1
Publications for gene IDH1 were changed from 22025298; 22057234 to 24049096; 22025298; 22057234; 22057236
Skeletal dysplasia v1.153 COL10A1 Eleanor Williams Added phenotypes Metaphyseal chondrodysplasia, Schmid type 156500 for gene: COL10A1
Skeletal dysplasia v1.153 MMP9 Eleanor Williams Added phenotypes Metaphyseal anadysplasia 2 613073 for gene: MMP9
Publications for gene MMP9 were changed from to 28342220; 24781753; 19615667
Skeletal dysplasia v1.153 MMP13 Eleanor Williams Added phenotypes Metaphyseal anadysplasia 1 602111; Spondyloepimetaphyseal dysplasia, Missouri type 602111; Metaphyseal dysplasia, Spahr type - 250400 for gene: MMP13
Publications for gene MMP13 were changed from to 24648384
Skeletal dysplasia v1.153 FGF16 Eleanor Williams Added phenotypes Metacarpal 4-5 fusion 309630 for gene: FGF16
Skeletal dysplasia v1.153 SULF1 Eleanor Williams Added phenotypes Mesomelia-synostoses syndrome 600383 for gene: SULF1
Skeletal dysplasia v1.153 SLCO5A1 Eleanor Williams Added phenotypes Mesomelia-synostoses syndrome 600383 for gene: SLCO5A1
Skeletal dysplasia v1.153 KAT6A Eleanor Williams Added phenotypes Mental retardation, autosomal dominant 32 - 616268 for gene: KAT6A
Skeletal dysplasia v1.153 ATP7A Eleanor Williams Added phenotypes Spinal muscular atrophy, distal, 300489; Menkes disease 309400; Occipital horn syndrome 304150 for gene: ATP7A
Skeletal dysplasia v1.153 FLNA Eleanor Williams Added phenotypes Terminal osseous dysplasia 300244; Melnick Needles syndrome 309350; Frontometaphyseal dysplasia 305620; Otopalatodigital syndrome, type II -304120; Otopalatodigital syndrome, type I -311300 for gene: FLNA
Skeletal dysplasia v1.153 CDC45 Eleanor Williams Added phenotypes Craniosynostosis (Wilkie) (from Ana Beleza); Meier-Gorlin syndrome with craniosynostosis (from PMID 27374770) for gene: CDC45
Skeletal dysplasia v1.153 CDT1 Eleanor Williams Added phenotypes Meier-Gorlin syndrome 4 613804 for gene: CDT1
Skeletal dysplasia v1.153 ORC6 Eleanor Williams Added phenotypes Meier-Gorlin syndrome 3 613803 for gene: ORC6
Skeletal dysplasia v1.153 ORC4 Eleanor Williams Added phenotypes Meier-Gorlin syndrome 2 613800 for gene: ORC4
Skeletal dysplasia v1.153 ORC1 Eleanor Williams Added phenotypes Meier-Gorlin syndrome 1 224690 for gene: ORC1
Skeletal dysplasia v1.153 COL9A3 Eleanor Williams Added phenotypes MED; multiple epiphyseal dysplasia 3, with or without myopathy - 600969 for gene: COL9A3
Skeletal dysplasia v1.153 B9D1 Eleanor Williams Added phenotypes Meckel syndrome 9 614209 for gene: B9D1
Publications for gene B9D1 were changed from 24886560; 21493627 to 21493627; 24886560
Skeletal dysplasia v1.153 TCTN2 Eleanor Williams Added phenotypes Joubert syndrome 24 616654; Meckel syndrome 8 613885 for gene: TCTN2
Skeletal dysplasia v1.153 CC2D2A Eleanor Williams Added phenotypes Meckel syndrome 6 612284 for gene: CC2D2A
Publications for gene CC2D2A were changed from 18513680; 24706459; 23351400 to 23351400; 24706459; 18513680
Skeletal dysplasia v1.153 GNAS Eleanor Williams Added phenotypes Pseudohypoparathyroidism Ia 103580; Pseudohypoparathyroidism Ib 603233; Osseous heteroplasia, progressive 166350; McCune-Albright syndrome, somatic, mosaic 174800 for gene: GNAS
Skeletal dysplasia v1.153 NFIX Eleanor Williams Added phenotypes Marshall-Smith syndrome 602535; Sotos syndrome 2 614753 for gene: NFIX
Skeletal dysplasia v1.153 MAN2B1 Eleanor Williams Added phenotypes Mannosidosis, alpha-, types I and II 248500 for gene: MAN2B1
Skeletal dysplasia v1.153 EFTUD2 Eleanor Williams Added phenotypes Mandibulofacial dysostosis, Guion-Almeida type 610536 for gene: EFTUD2
Publications for gene EFTUD2 were changed from 19334086; 16760738; 22305528 to 16760738; 19334086; 22305528
Skeletal dysplasia v1.153 ZMPSTE24 Eleanor Williams Added phenotypes Mandibuloacral dysplasia with type B lipodystrophy 608612; Restrictive dermopathy, lethal 275210 for gene: ZMPSTE24
Skeletal dysplasia v1.153 LMNA Eleanor Williams Added phenotypes Heart-hand syndrome, Slovenian type 610140; 616516; Hutchinson-Gilford progeria 176670; Mandibuloacral dysplasia 248370 for gene: LMNA
Skeletal dysplasia v1.153 LPIN2 Eleanor Williams Added phenotypes Majeed syndrome (Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia) 609628 for gene: LPIN2
Publications for gene LPIN2 were changed from to 29912021
Skeletal dysplasia v1.153 FBLIM1 Eleanor Williams Added phenotypes Majeed syndrome (Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia) 609628 for gene: FBLIM1
Publications for gene FBLIM1 were changed from to 29912021
Skeletal dysplasia v1.153 SETD2 Eleanor Williams Added phenotypes Luscan-Lumish syndrome 616831 for gene: SETD2
Skeletal dysplasia v1.153 TGFB2 Eleanor Williams Added phenotypes Loeys-Dietz syndrome 4 614816 for gene: TGFB2
Skeletal dysplasia v1.153 SMAD3 Eleanor Williams Added phenotypes Loeys-Dietz syndrome 3 613795 for gene: SMAD3
Skeletal dysplasia v1.153 TGFBR2 Eleanor Williams Added phenotypes Loeys-Dietz syndrome 2 610168 for gene: TGFBR2
Skeletal dysplasia v1.153 TGFBR1 Eleanor Williams Added phenotypes Loeys-Dietz syndrome 1 609192 for gene: TGFBR1
Skeletal dysplasia v1.153 FERMT3 Eleanor Williams Added phenotypes Leukocyte adhesion deficiency, type III 612840 for gene: FERMT3
Publications for gene FERMT3 were changed from to 18709451
Skeletal dysplasia v1.153 PTPN11 Eleanor Williams Added phenotypes Metachondromatosis 156250; LEOPARD syndrome 1 151100; Noonan syndrome 1 163950 for gene: PTPN11
Skeletal dysplasia v1.153 PTDSS1 Eleanor Williams Added phenotypes Lenz-Majewski hyperostotic dwarfism 151050 for gene: PTDSS1
Skeletal dysplasia v1.153 GZF1 Eleanor Williams Added phenotypes Larsen syndrome for gene: GZF1
Skeletal dysplasia v1.153 B3GAT3 Eleanor Williams Added phenotypes Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects, 245600; Larsen alike phenotype (skd incl) for gene: B3GAT3
Skeletal dysplasia v1.153 GHR Eleanor Williams Added phenotypes increased responsiveness to growth hormone 604271; Laron dwarfism, 262500; Growth hormone insensitivity for gene: GHR
Skeletal dysplasia v1.153 SHOX Eleanor Williams Added phenotypes Langer mesomelic dysplasia 249700; Short stature, idiopathic familial 300582; Leri-Weill dyschondrosteosis 127300 for gene: SHOX
Skeletal dysplasia v1.153 FGF10 Eleanor Williams Added phenotypes LADD syndrome 149730 for gene: FGF10
Skeletal dysplasia v1.153 MEOX1 Eleanor Williams Added phenotypes Klippel-Feil syndrome 2 214300 for gene: MEOX1
Skeletal dysplasia v1.153 GDF6 Eleanor Williams Added phenotypes Klippel-Feil syndrome 1, autosomal dominant 118100; Multiple synostoses syndrome type 4 - 617898. for gene: GDF6
Publications for gene GDF6 were changed from to 18425797
Skeletal dysplasia v1.153 GDF3 Eleanor Williams Added phenotypes Klippel-Feil anomaly with laryngeal malformation - 613702 for gene: GDF3
Publications for gene GDF3 were changed from to 19864492
Skeletal dysplasia v1.153 MGP Eleanor Williams Added phenotypes Keutel syndrome 245150 for gene: MGP
Skeletal dysplasia v1.153 ANKRD11 Eleanor Williams Added phenotypes KBG syndrome 148050 for gene: ANKRD11
Skeletal dysplasia v1.153 KMT2D Eleanor Williams Added phenotypes Kabuki syndrome 1 - 147920 for gene: KMT2D
Skeletal dysplasia v1.153 CSPP1 Eleanor Williams Added phenotypes ORPHA:397715 Joubert syndrome with Jeune asphyxiating thoracic dystrophy; ORPHA:475 Joubert syndrome; ORPHA:564 Meckel syndrome; Joubert syndrome 21 615636 for gene: CSPP1
Publications for gene CSPP1 were changed from to 24360808; 24360803
Skeletal dysplasia v1.153 TMEM231 Eleanor Williams Added phenotypes Joubert syndrome 20 614970; Meckel syndrome 11 615397 for gene: TMEM231
Skeletal dysplasia v1.153 TMEM216 Eleanor Williams Added phenotypes Meckel syndrome 2 603194; Joubert syndrome 2 608091 for gene: TMEM216
Skeletal dysplasia v1.153 TCTN3 Eleanor Williams Added phenotypes Orofaciodigital syndrome IV 258860; Joubert syndrome 18 614815 for gene: TCTN3
Skeletal dysplasia v1.153 OFD1 Eleanor Williams Added phenotypes Joubert syndrome 10 300804; Simpson-Golabi-Behmel syndrome, type 2 300209 XLR; Orofaciodigital syndrome I 311200 XLD for gene: OFD1
Skeletal dysplasia v1.153 TBX4 Eleanor Williams Added phenotypes Ischiocoxopodopatellar syndrome 147891 for gene: TBX4
Skeletal dysplasia v1.153 IL1RN Eleanor Williams Added phenotypes Interleukin 1 receptor antagonist deficiency 612852 for gene: IL1RN
Skeletal dysplasia v1.153 EXTL3 Eleanor Williams Added phenotypes Immunoskeletal dysplasia with neurodevelopmental abnormalities 617425 for gene: EXTL3
Skeletal dysplasia v1.153 PGM3 Eleanor Williams Added phenotypes Immunodeficiency 23 615816 for gene: PGM3
Skeletal dysplasia v1.153 CDKN1C Eleanor Williams Added phenotypes IMAGE syndrome 614732 for gene: CDKN1C
Skeletal dysplasia v1.153 PHEX Eleanor Williams Added phenotypes Hypophosphatemic rickets, X-linked dominant 307800 for gene: PHEX
Skeletal dysplasia v1.153 FGF23 Eleanor Williams Added phenotypes Hypophosphatemic rickets, autosomal dominant 193100 for gene: FGF23
Skeletal dysplasia v1.153 DMP1 Eleanor Williams Added phenotypes Hypophosphatemic rickets, AR, 241520 for gene: DMP1
Skeletal dysplasia v1.153 SLC34A3 Eleanor Williams Added phenotypes Hypophosphatemic rickets with hypercalciuria 241530 for gene: SLC34A3
Skeletal dysplasia v1.153 ALPL Eleanor Williams Added phenotypes hypophosphatasia; skeletal dysplasias; Osteogenesis Imperfecta and Decreased Bone Density for gene: ALPL
Skeletal dysplasia v1.153 TBCE Eleanor Williams Added phenotypes Hypoparathyroidism-retardation-dysmorphism syndrome 241410; Kenny-Caffey syndrome, type 1 244460. for gene: TBCE
Skeletal dysplasia v1.153 SLCO2A1 Eleanor Williams Added phenotypes Hypertrophic osteoarthropathy, primary, autosomal recessive 2 614441 for gene: SLCO2A1
Skeletal dysplasia v1.153 ABCC9 Eleanor Williams Added phenotypes Hypertrichotic osteochondrodysplasia 23985 (Cantu syndrome) for gene: ABCC9
Skeletal dysplasia v1.153 PDE3A Eleanor Williams Added phenotypes Hypertension and brachydactyly syndrome, 112410 for gene: PDE3A
Skeletal dysplasia v1.153 PIGV Eleanor Williams Added phenotypes Hyperphosphatasia with mental retardation syndrome 1 239300 for gene: PIGV
Skeletal dysplasia v1.153 CASR Eleanor Williams Added phenotypes Hypocalcemia, autosomal dominant 601198; Hypocalciuric hypercalcemia, type I 145980; Hyperparathyroidism, neonatal 239200; Hypocalcemia, autosomal dominant, with Bartter syndrome 601198 for gene: CASR
Skeletal dysplasia v1.153 LRP5 Eleanor Williams Added phenotypes [Bone mineral density variability 1] 601884; Osteopetrosis, autosomal dominant 1 607634; Osteosclerosis 144750; van Buchem disease, type 2 607636; Osteoporosis-pseudoglioma syndrome 259770; Hyperostosis, endosteal 144750; {Osteoporosis} 166710 for gene: LRP5
Skeletal dysplasia v1.153 ANTXR2 Eleanor Williams Added phenotypes Hyaline fibromatosis syndrome 228600 for gene: ANTXR2
Skeletal dysplasia v1.153 TBX5 Eleanor Williams Added phenotypes Holt-Oram syndrome 142900 for gene: TBX5
Skeletal dysplasia v1.153 SLC29A3 Eleanor Williams Added phenotypes Histiocytosis-lymphadenopathy plus syndrome 602782 for gene: SLC29A3
Skeletal dysplasia v1.153 FGFR1 Eleanor Williams Added phenotypes Osteoglophonic dysplasia 166250; Hartsfield syndrome 615465; Jackson-Weiss syndrome 123150; Pfeiffer syndrome 101600; Trigonocephaly 1 190440 for gene: FGFR1
Skeletal dysplasia v1.153 CTSC Eleanor Williams Added phenotypes Haim-Munk syndrome 245010, for gene: CTSC
Skeletal dysplasia v1.153 OAT Eleanor Williams Added phenotypes Gyrate atrophy of choroid and retina with or without ornithinemia 258870 for gene: OAT
Skeletal dysplasia v1.153 HOXA13 Eleanor Williams Added phenotypes Hand-foot-uterus syndrome 140000; Guttmacher syndrome 176305 for gene: HOXA13
Skeletal dysplasia v1.153 GLI3 Eleanor Williams Added phenotypes Greig cephalopolysyndactyly syndrome 175700; Polydactyly, postaxial, types A1 and B 174200; Polydactyly, preaxial, type IV 174700; Pallister-Hall syndrome 146510; {Hypothalamic hamartomas, somatic} 241800 for gene: GLI3
Skeletal dysplasia v1.153 LBR Eleanor Williams Added phenotypes Pelger-Huet anomaly with mild skeletal anomalies 618019; Greenberg skeletal dysplasia 215140; Pelger-Huet anomaly 169400 for gene: LBR
Skeletal dysplasia v1.153 FAM111A Eleanor Williams Added phenotypes Gracile bone dysplasia 602361; Kenny-Caffey syndrome, type 2 127000 for gene: FAM111A
Skeletal dysplasia v1.153 ANO5 Eleanor Williams Added phenotypes Gnatodiaphyseal dysplasia; Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias; Disproportionate Short Stature for gene: ANO5
Skeletal dysplasia v1.153 GLB1 Eleanor Williams Added phenotypes GM1-gangliosidosis, type I 230500; Mucopolysaccharidosis type IVB (Morquio) 253010 for gene: GLB1
Skeletal dysplasia v1.153 TBXAS1 Eleanor Williams Added phenotypes Ghosal hematodiaphyseal syndrome 231095 for gene: TBXAS1
Skeletal dysplasia v1.153 GORAB Eleanor Williams Added phenotypes Geroderma osteodysplasticum 231070 for gene: GORAB
Skeletal dysplasia v1.153 KAT6B Eleanor Williams Added phenotypes SBBYSS syndrome 603736; Genitopatellar syndrome 606170 for gene: KAT6B
Skeletal dysplasia v1.153 LTBP3 Eleanor Williams Added phenotypes Dental anomalies and short stature 610216; Geleophysic dysplasia 3 617809 for gene: LTBP3
Skeletal dysplasia v1.153 ADAMTSL2 Eleanor Williams Added phenotypes Geleophysic dysplasia 1 231050 for gene: ADAMTSL2
Skeletal dysplasia v1.153 DCC Eleanor Williams Added phenotypes Gaze palsy, familial horizontal, with progressive scoliosis, 2 617542 for gene: DCC
Skeletal dysplasia v1.153 CTSA Eleanor Williams Added phenotypes Galactosialidosis 256540 for gene: CTSA
Skeletal dysplasia v1.153 WNT7A Eleanor Williams Added phenotypes Ulna and fibula, absence of, with severe limb deficiency 276820; Fuhrmann syndrome 228930 for gene: WNT7A
Skeletal dysplasia v1.153 FUCA1 Eleanor Williams Added phenotypes Fucosidosis 230000 for gene: FUCA1
Skeletal dysplasia v1.153 ALX1 Eleanor Williams Added phenotypes Frontonasal dysplasia type 3 613456 for gene: ALX1
Skeletal dysplasia v1.153 ALX4 Eleanor Williams Added phenotypes Frontonasal dysplasia 2 613451 for gene: ALX4
Skeletal dysplasia v1.153 ALX3 Eleanor Williams Added phenotypes Frontonasal dysplasia 1 136760 (frontorhiny) for gene: ALX3
Skeletal dysplasia v1.153 MAP3K7 Eleanor Williams Added phenotypes Frontometaphyseal dysplasia 2, 617137 for gene: MAP3K7
Skeletal dysplasia v1.153 SH3PXD2B Eleanor Williams Added phenotypes Frank-ter Haar syndrome 249420 for gene: SH3PXD2B
Skeletal dysplasia v1.153 GSC Eleanor Williams Added phenotypes Foundation Trust) Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities 602471 for gene: GSC
Skeletal dysplasia v1.153 ACVR1 Eleanor Williams Added phenotypes Fibrodysplasia ossificans progressiva 135100 for gene: ACVR1
Skeletal dysplasia v1.153 COL11A2 Eleanor Williams Added phenotypes Stickler syndrome, type III 184840; Otospondylomegaepiphyseal dysplasia 215150; Fibrochondrogenesis 2 614524? for gene: COL11A2
Skeletal dysplasia v1.153 COL11A1 Eleanor Williams Added phenotypes Stickler syndrome, type II 604841; Marshall syndrome 154780; Fibrochondrogenesis 1 228520 for gene: COL11A1
Skeletal dysplasia v1.153 MIR17HG Eleanor Williams Added phenotypes Feingold syndrome 2, 614326 for gene: MIR17HG
Publications for gene MIR17HG were changed from 21892160; 25391829; 19344873; 26360630 to 25391829; 21892160; 26360630; 19344873
Skeletal dysplasia v1.153 MYCN Eleanor Williams Added phenotypes Feingold syndrome (Microcephaly-oculo-digito-esophageal-duodenal) 164280 for gene: MYCN
Skeletal dysplasia v1.153 EXT2 Eleanor Williams Added phenotypes Exostoses, multiple, type 2 133701 for gene: EXT2
Skeletal dysplasia v1.153 EXT1 Eleanor Williams Added phenotypes trichorhinophalangeal syndrome type 2 -150230; Exostoses, multiple, type 13370 for gene: EXT1
Skeletal dysplasia v1.153 COL9A1 Eleanor Williams Added phenotypes Stickler syndrome, type IV 614134; Epiphyseal dysplasia, multiple, 6 614135 for gene: COL9A1
Skeletal dysplasia v1.153 MATN3 Eleanor Williams Added phenotypes Spondyloepimetaphyseal dysplasia, 608728; Epiphyseal dysplasia, multiple, 5, 607078 for gene: MATN3
Skeletal dysplasia v1.153 COMP Eleanor Williams Added phenotypes Epiphyseal dysplasia, multiple, 1 132400; Pseudoachondroplasia 177170 for gene: COMP
Skeletal dysplasia v1.153 ICK Eleanor Williams Added phenotypes Endocrine-cerebroosteodysplasia 612651 for gene: ICK
Skeletal dysplasia v1.153 IDH2 Eleanor Williams Added phenotypes Enchondromatosis (Ollier) and Enchondromatosis with hermangiomata (Maffucci) 166000, metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (614875) for gene: IDH2
Publications for gene IDH2 were changed from to 24049096; 22057234; 22057236
Skeletal dysplasia v1.153 EVC2 Eleanor Williams Added phenotypes Ellis-van Creveld syndrome 225500; Weyers acrofacial dysostosis 193530 for gene: EVC2
Skeletal dysplasia v1.153 B3GALT6 Eleanor Williams Added phenotypes Ehlers-Danlos syndrome, progeroid type, 2 615349; Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures 271640 for gene: B3GALT6
Skeletal dysplasia v1.153 CHST14 Eleanor Williams Added phenotypes Ehlers-Danlos syndrome, musculocontractural type 1 601776 for gene: CHST14
Skeletal dysplasia v1.153 COL1A2 Eleanor Williams Added phenotypes Ehlers-Danlos syndrome, cardiac valvular form 225320; Ehlers-Danlos syndrome, type VIIB 130060; Osteogenesis imperfecta, type II 166210; Osteogenesis imperfecta, type III 259420; Osteogenesis imperfecta, type IV 166220 for gene: COL1A2
Skeletal dysplasia v1.153 B4GALT7 Eleanor Williams Added phenotypes Ehlers-Danlos syndrome with short stature and limb anomalies 130070 for gene: B4GALT7
Skeletal dysplasia v1.153 EVC Eleanor Williams Added phenotypes ECV1; Ellis-van Creveld syndrome, 225500 for gene: EVC
Skeletal dysplasia v1.153 IKBKG Eleanor Williams Added phenotypes Incontinentia pigmenti 308300; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency 300301 for gene: IKBKG
Skeletal dysplasia v1.153 CDH3 Eleanor Williams Added phenotypes Ectodermal dysplasia, ectrodactyly, and macular dystrophy 225280 for gene: CDH3
Skeletal dysplasia v1.153 HSPG2 Eleanor Williams Added phenotypes Dyssegmental dysplasia, Silverman-Handmaker type 224410; Schwartz-Jampel syndrome, type 1 255800 for gene: HSPG2
Skeletal dysplasia v1.153 TERT Eleanor Williams Added phenotypes Dyskeratosis congenita, autosomal dominant 2 and autosomal recessive 4 613989 for gene: TERT
Skeletal dysplasia v1.153 DYM Eleanor Williams Added phenotypes Dyggve-Melchior-Clausen disease 223800; Smith-McCort dysplasia 607326 for gene: DYM
Skeletal dysplasia v1.153 BMPER Eleanor Williams Added phenotypes Diaphanospondylodysostosis 608022 for gene: BMPER
Skeletal dysplasia v1.153 DHCR24 Eleanor Williams Added phenotypes Desmosterolosis 602398 for gene: DHCR24
Skeletal dysplasia v1.153 XYLT1 Eleanor Williams Added phenotypes Desbuquois dysplasia 2 615777 for gene: XYLT1
Skeletal dysplasia v1.153 CANT1 Eleanor Williams Added phenotypes Desbuquois dysplasia 1 251450; multiple epiphyseal dysplasia type 7, 617719. for gene: CANT1
Skeletal dysplasia v1.153 CLCN5 Eleanor Williams Added phenotypes Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis 308990; Dent disease 300009; Nephrolithiasis, type I 310468; Hypophosphatemic rickets 300554 for gene: CLCN5
Skeletal dysplasia v1.153 PYCR1 Eleanor Williams Added phenotypes Cutis laxa, autosomal recessive, type IIB 612940; Cutis laxa, autosomal recessive, type IIIB 614438 for gene: PYCR1
Skeletal dysplasia v1.153 ATP6V0A2 Eleanor Williams Added phenotypes Cutis laxa, autosomal recessive, type IIA 219200 for gene: ATP6V0A2
Skeletal dysplasia v1.153 MNX1 Eleanor Williams Added phenotypes Currarino syndrome 176450 for gene: MNX1
Skeletal dysplasia v1.153 MSX2 Eleanor Williams Added phenotypes Craniosynostosis, type 2 604757; Parietal foramina with cleidocranial dysplasia 168550; Parietal foramina 1 168500 for gene: MSX2
Skeletal dysplasia v1.153 TWIST1 Eleanor Williams Added phenotypes Robinow-Sorauf syndrome 180750; Saethre-Chotzen syndrome 101400; Craniosynostosis, type 1 123100; Saethre-Chotzen syndrome with eyelid anomalies 101400 for gene: TWIST1
Skeletal dysplasia v1.153 IL11RA Eleanor Williams Added phenotypes Craniosynostosis and dental anomalies 614188 for gene: IL11RA
Skeletal dysplasia v1.153 ZIC1 Eleanor Williams Added phenotypes Craniosynostosis 6 616602 for gene: ZIC1
Skeletal dysplasia v1.153 ERF Eleanor Williams Added phenotypes Chitayat syndrome - 617180; Craniosynostosis 4 600775 for gene: ERF
Skeletal dysplasia v1.153 TCF12 Eleanor Williams Added phenotypes Craniosynostosis 3 615314 for gene: TCF12
Skeletal dysplasia v1.153 HPGD Eleanor Williams Added phenotypes Cranioosteoarthropathy 259100; Digital clubbing, isolated congenital 119900; Hypertrophic osteoarthropathy, primary, autosomal recessive 1 259100 for gene: HPGD
Skeletal dysplasia v1.153 GJA1 Eleanor Williams Added phenotypes Oculodentodigital dysplasia 164200; Syndactyly, type III 186100; Erythrokeratodermia variabilis et progressiva 133200; Palmoplantar keratoderma with congenital alopecia 104100; Oculodentodigital dysplasia, autosomal recessive 257850; Craniometaphyseal dysplasia, autosomal recessive 218400; Hypoplastic left heart syndrome 1 241550 for gene: GJA1
Skeletal dysplasia v1.153 EFNB1 Eleanor Williams Added phenotypes Craniofrontonasal dysplasia 304110 for gene: EFNB1
Skeletal dysplasia v1.153 TMCO1 Eleanor Williams Added phenotypes Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome 213980 for gene: TMCO1
Skeletal dysplasia v1.153 WDR35 Eleanor Williams Added phenotypes Short-rib thoracic dysplasia 7 with or without polydactyly 614091; Cranioectodermal dysplasia 2 613610 for gene: WDR35
Skeletal dysplasia v1.153 IFT122 Eleanor Williams Added phenotypes Cranioectodermal dysplasia 1 218330 for gene: IFT122
Skeletal dysplasia v1.153 SOST Eleanor Williams Added phenotypes Craniodiaphyseal dysplasia, autosomal dominant 122860; Van Buchem disease 239100; Sclerosteosis 1 269500 for gene: SOST
Skeletal dysplasia v1.153 AKT1 Eleanor Williams Added phenotypes Proteus syndrome, somatic 176920; Cowden syndrome 6 615109 for gene: AKT1
Skeletal dysplasia v1.153 TBX15 Eleanor Williams Added phenotypes Cousin syndrome 260660 for gene: TBX15
Skeletal dysplasia v1.153 HDAC8 Eleanor Williams Added phenotypes Wilson-Turner syndrome 309585; Cornelia de Lange syndrome 5 300882 for gene: HDAC8
Skeletal dysplasia v1.153 RAD21 Eleanor Williams Added phenotypes Cornelia de Lange syndrome 4 614701 for gene: RAD21
Skeletal dysplasia v1.153 SMC3 Eleanor Williams Added phenotypes Cornelia de Lange syndrome 3 610759 for gene: SMC3
Skeletal dysplasia v1.153 SMC1A Eleanor Williams Added phenotypes Cornelia de Lange syndrome 2 300590 for gene: SMC1A
Skeletal dysplasia v1.153 NIPBL Eleanor Williams Added phenotypes Cornelia de Lange syndrome 1 122470 for gene: NIPBL
Skeletal dysplasia v1.153 FBN2 Eleanor Williams Added phenotypes Contractural arachnodactyly, congenital 121050 for gene: FBN2
Skeletal dysplasia v1.153 NSDHL Eleanor Williams Added phenotypes Congenital hemidysplasia, ichthyosis, limb defects (CHILD) syndrome 308050; CK syndrome 300831 for gene: NSDHL
Skeletal dysplasia v1.153 ABL1 Eleanor Williams Added phenotypes Congenital heart defects and skeletal malformations syndrome, 617602 for gene: ABL1
Skeletal dysplasia v1.153 RFT1 Eleanor Williams Added phenotypes Congenital disorder of glycosylation, type In 612015 for gene: RFT1
Skeletal dysplasia v1.153 ALG9 Eleanor Williams Added phenotypes Gillessen-Kaesbach-Nishimura syndrome 263210; Congenital disorder of glycosylation, type Il 608776 for gene: ALG9
Skeletal dysplasia v1.153 TMEM165 Eleanor Williams Added phenotypes Congenital disorder of glycosylation, type IIk 614727 for gene: TMEM165
Skeletal dysplasia v1.153 COG1 Eleanor Williams Added phenotypes Congenital disorder of glycosylation, type IIg 611209 for gene: COG1
Publications for gene COG1 were changed from to 16537452; 19008299
Skeletal dysplasia v1.153 ALG12 Eleanor Williams Added phenotypes Congenital disorder of glycosylation, type Ig 607143 for gene: ALG12
Skeletal dysplasia v1.153 MPDU1 Eleanor Williams Added phenotypes Congenital disorder of glycosylation, type If 609180 for gene: MPDU1
Skeletal dysplasia v1.153 DPM1 Eleanor Williams Added phenotypes Congenital disorder of glycosylation, type Ie 608799 for gene: DPM1
Publications for gene DPM1 were changed from to 23856421; 10642602; 15669674
Skeletal dysplasia v1.153 ALG3 Eleanor Williams Added phenotypes Congenital disorder of glycosylation, type Id 601110 for gene: ALG3
Skeletal dysplasia v1.153 SEC24D Eleanor Williams Added phenotypes Osteogenesis Imperfecta, Cole Carpenter syndrome; Cole-Carpenter syndrome; SYNDROMIC OSTEOGENESIS IMPERFECTA for gene: SEC24D
Skeletal dysplasia v1.153 P4HB Eleanor Williams Added phenotypes Cole-Carpenter syndrome 1 112240 for gene: P4HB
Publications for gene P4HB were changed from 25683117 to 29384951; 30063094; 25683117
Skeletal dysplasia v1.153 ENPP1 Eleanor Williams Added phenotypes Hypophosphatemic rickets, autosomal recessive, 2 613312; Cole disease 615522 for gene: ENPP1
Skeletal dysplasia v1.153 EED Eleanor Williams Added phenotypes Cohen-Gibson syndrome 617561 for gene: EED
Publications for gene EED were changed from 25787343; 27193220; 27868325; 28229514 to 25787343; 27193220; 27868325; 28229514
Skeletal dysplasia v1.153 ARID1B Eleanor Williams Added phenotypes Coffin-Siris syndrome type 1 - 135900 for gene: ARID1B
Skeletal dysplasia v1.153 LONP1 Eleanor Williams Added phenotypes CODAS (Cerebral, Ocular, Dental, Auricular and Skeletal anomalies) syndrome 600373 for gene: LONP1
Skeletal dysplasia v1.153 RPGRIP1L Eleanor Williams Added phenotypes COACH syndrome 216360; Meckel syndrome 5 611561; Joubert syndrome 7 611560 for gene: RPGRIP1L
Skeletal dysplasia v1.153 TMEM67 Eleanor Williams Added phenotypes COACH syndrome 216360; Meckel syndrome 3 607361; Joubert syndrome 6 610688; {Bardet-Biedl syndrome 14, modifier of} 615991 for gene: TMEM67
Skeletal dysplasia v1.153 PITX1 Eleanor Williams Added phenotypes Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 119800; Liebenberg syndrome 186550 for gene: PITX1
Publications for gene PITX1 were changed from 23587911; 23022097 to 30459804; 23022097; 23587911
Skeletal dysplasia v1.153 PIK3CA Eleanor Williams Added phenotypes CLOVES 612918 for gene: PIK3CA
Skeletal dysplasia v1.153 RUNX2 Eleanor Williams Added phenotypes Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 156510; Cleidocranial dysplasia, forme fruste, with brachydactyly 119600; Cleidocranial dysplasia, forme fruste, dental anomalies only 119600; Cleidocranial dysplasia 119600 for gene: RUNX2
Skeletal dysplasia v1.153 NLRP3 Eleanor Williams Added phenotypes Chronic infantile neurologic cutaneous articular syndrome (CINA) - 607115 for gene: NLRP3
Skeletal dysplasia v1.153 PTH1R Eleanor Williams Added phenotypes Failure of tooth eruption, primary 125350; Eiken syndrome 600002; Metaphyseal chondrodysplasia, Murk Jansen type 156400; Chondrodysplasia, Blomstrand type 215045 for gene: PTH1R
Skeletal dysplasia v1.153 IMPAD1 Eleanor Williams Added phenotypes Chondrodysplasia with joint dislocations, GPAPP type 614078 for gene: IMPAD1
Skeletal dysplasia v1.153 ANKH Eleanor Williams Added phenotypes Chondrocalcinosis 2 118600; Craniometaphyseal dysplasia 123000 for gene: ANKH
Skeletal dysplasia v1.153 SH3BP2 Eleanor Williams Added phenotypes Cherubism 118400 for gene: SH3BP2
Skeletal dysplasia v1.153 SNRPB Eleanor Williams Added phenotypes Cerebrocostomandibular syndrome 117650 for gene: SNRPB
Skeletal dysplasia v1.153 LRP4 Eleanor Williams Added phenotypes Sclerosteosis 2 614305; Cenani-Lenz syndactyly syndrome 212780 for gene: LRP4
Skeletal dysplasia v1.153 EBP Eleanor Williams Added phenotypes MEND syndrome-300960 XLR.; CDPXLD; Chondrodysplasia punctata, X-linked dominant, 302960 for gene: EBP
Skeletal dysplasia v1.153 ARSE Eleanor Williams Added phenotypes CDPXL; Chondrodysplasia punctata, X-linked recessive, 302950; CHONDRODYSPLASIA PUNCTATA 1, X-LINKED; X-linked recessive chondrodysplasia punctata for gene: ARSE
Skeletal dysplasia v1.153 TGDS Eleanor Williams Added phenotypes Catel-Manzke syndrome 616145 for gene: TGDS
Skeletal dysplasia v1.153 RAB23 Eleanor Williams Added phenotypes Carpenter syndrome 201000 for gene: RAB23
Skeletal dysplasia v1.153 MEGF8 Eleanor Williams Added phenotypes Carpenter syndrome 2 614976 for gene: MEGF8
Skeletal dysplasia v1.153 TGFB1 Eleanor Williams Added phenotypes Camurati-Engelmann disease 131300 for gene: TGFB1
Skeletal dysplasia v1.153 COL1A1 Eleanor Williams Added phenotypes Osteogenesis imperfecta, type I 166200; Caffey disease 114000; Osteogenesis imperfecta, type III 259420; Osteogenesis imperfecta, type II 166210; Ehlers-Danlos syndrome, type VIIA 130060; Ehlers-Danlos syndrome, classic 130000; Osteogenesis imperfecta, type IV 166220 for gene: COL1A1
Skeletal dysplasia v1.153 CD96 Eleanor Williams Added phenotypes C-syndrome 217750 (opitz trigonocephaly) for gene: CD96
Skeletal dysplasia v1.153 LEMD3 Eleanor Williams Added phenotypes Melorheostosis with osteopoikilosis 155950 IC; Osteopoikilosis 166700; Buschke-Ollendorff syndrome 166700 for gene: LEMD3
Skeletal dysplasia v1.153 FKBP10 Eleanor Williams Added phenotypes Brucks syndrome 1 - 259450; Osteogenesis imperfecta, type XI, 610968 for gene: FKBP10
Skeletal dysplasia v1.153 PLOD2 Eleanor Williams Added phenotypes Bruck syndrome 2 609220 for gene: PLOD2
Skeletal dysplasia v1.153 TRPV4 Eleanor Williams Added phenotypes Brachyolmia type 3 113500; Hereditary motor and sensory neuropathy, type IIc 606071; Digital arthropathy-brachydactyly, familial 606835; SED, Maroteaux type 184095; Parastremmatic dwarfism 168400; Metatropic dysplasia 156530; Scapuloperoneal spinal muscular atrophy 181405; Spinal muscular atrophy, distal, congenital nonprogressive 600175; Spondylometaphyseal dysplasia, Kozlowski type 184252 for gene: TRPV4
Skeletal dysplasia v1.153 PAPSS2 Eleanor Williams Added phenotypes Brachyolmia 4 with mild epiphyseal and metaphyseal changes 612847 for gene: PAPSS2
Skeletal dysplasia v1.153 PTHLH Eleanor Williams Added phenotypes Brachydactyly, type E2 613382 for gene: PTHLH
Skeletal dysplasia v1.153 NOG Eleanor Williams Added phenotypes Symphalangism, proximal, 1A 185800; Brachydactyly, type B2 611377; Tarsal-carpal coalition syndrome 186570; Stapes ankylosis with broad thumb and toes 184460; Multiple synostoses syndrome 1 186500 for gene: NOG
Skeletal dysplasia v1.153 ROR2 Eleanor Williams Added phenotypes Brachydactyly, type B1 113000; Robinow syndrome, autosomal recessive 268310 for gene: ROR2
Skeletal dysplasia v1.153 BMP2 Eleanor Williams Added phenotypes short stature, facial dysmorphism and skeletal anomalies with or without cardiac aomalies 617877.; Brachydactyly, type A2 112600; {HFE hemochromatosis, modifier of} 235200 for gene: BMP2
Skeletal dysplasia v1.153 HOXD13 Eleanor Williams Added phenotypes Syndactyly, type V 186300; Brachydactyly-syndactyly syndrome 610713; Brachydactyly, type E 113300; Synpolydactyly 1 186000; Brachydactyly, type D 113200 for gene: HOXD13
Skeletal dysplasia v1.153 PLS3 Eleanor Williams Added phenotypes Bone mineral density QTL18, osteoporosis 300910 for gene: PLS3
Skeletal dysplasia v1.153 ASXL1 Eleanor Williams Added phenotypes Bohring-Opitz syndrome 605039 for gene: ASXL1
Skeletal dysplasia v1.153 RASGRP2 Eleanor Williams Added phenotypes Bleeding disorder, platelet-type, 18 615888 for gene: RASGRP2
Publications for gene RASGRP2 were changed from 18709451; 24958846 to 24958846; 18709451
Skeletal dysplasia v1.153 UFSP2 Eleanor Williams Added phenotypes Beukes Hip Dysplasia 142669, Spondyloepimetaphyseal dysplasia, Di Rocco type 617974 for gene: UFSP2
Publications for gene UFSP2 were changed from to 28892125; 26428751
Skeletal dysplasia v1.153 MANBA Eleanor Williams Added phenotypes Beta-mannosidosis, 248510 for gene: MANBA
Skeletal dysplasia v1.153 CEP290 Eleanor Williams Added phenotypes Meckel syndrome 4 611134; Senior-Loken syndrome 6 610189; Joubert syndrome 5 610188; Bardet-Biedl syndrome 14 615991; Leber congenital amaurosis 10 for gene: CEP290
Skeletal dysplasia v1.153 MKS1 Eleanor Williams Added phenotypes Meckel syndrome 1 249000; Bardet-Biedl syndrome 13 615990 for gene: MKS1
Skeletal dysplasia v1.153 RECQL4 Eleanor Williams Added phenotypes RAPILINO syndrome 266280; Rothmund-Thomson syndrome 268400; Baller-Gerold syndrome 218600 for gene: RECQL4
Skeletal dysplasia v1.153 FZD2 Eleanor Williams Added phenotypes Autosomal dominant omodysplasia type 2 164745 for gene: FZD2
Publications for gene FZD2 were changed from 25759469 to 29230162; 30455931; 29383834; 29383830; 25759469
Skeletal dysplasia v1.153 HNRNPK Eleanor Williams Added phenotypes Au-Kline syndrome:616580; Orphanet:453499 for gene: HNRNPK
Publications for gene HNRNPK were changed from 26173930; 26954065; 26638989 to 26173930; 26638989; 26954065
Skeletal dysplasia v1.153 FLNB Eleanor Williams Added phenotypes Spondylocarpotarsal synostosis syndrome 272460; Atelosteogenesis, type III 108721; Boomerang dysplasia 112310; Atelosteogenesis, type I 108720; Larsen syndrome 150250 for gene: FLNB
Skeletal dysplasia v1.153 AGA Eleanor Williams Added phenotypes Aspartylglucosaminuria 208400 (Patients may be tall for their age, but lack of a growth spurt in puberty typically causes adults to be short) for gene: AGA
Skeletal dysplasia v1.153 WISP3 Eleanor Williams Added phenotypes Arthropathy, progressive pseudorheumatoid, of childhood 208230; Spondyloepiphyseal dysplasia tarda with progressive arthropathy 208230 for gene: WISP3
Skeletal dysplasia v1.153 FGFR2 Eleanor Williams Added phenotypes Beare-Stevenson cutis gyrata syndrome 123790; Craniosynostosis, nonspecific Crouzon syndrome 123500; Craniofacial-skeletal-dermatologic dysplasia 101600; Pfeiffer syndrome 101600; Gastric cancer, somatic 613659; Jackson-Weiss syndrome 123150; LADD syndrome 149730; Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 207410; Apert syndrome 101200; Bent bone dysplasia syndrome 614592 for gene: FGFR2
Skeletal dysplasia v1.153 POR Eleanor Williams Added phenotypes Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571 for gene: POR
Skeletal dysplasia v1.153 RMRP Eleanor Williams Added phenotypes Cartilage-hair hypoplasia 250250; Anauxetic dysplasia 607095; Metaphyseal dysplasia without hypotrichosis 250460 for gene: RMRP
Skeletal dysplasia v1.153 POP1 Eleanor Williams Added phenotypes Anauxetic dysplasia 2, 617396 for gene: POP1
Publications for gene POP1 were changed from 21455487; 27380734; 28067412 to 28067412; 21455487; 27380734
Skeletal dysplasia v1.153 DLX3 Eleanor Williams Added phenotypes Amelogenesis imperfecta, type IV 104510; Trichodontoosseous syndrome 190320 for gene: DLX3
Publications for gene DLX3 were changed from 26762616; 26104267 to 26104267; 26762616
Skeletal dysplasia v1.153 HDAC4 Eleanor Williams Added phenotypes Albright hereditary osteodystrophy type 3; Brachydactyly-intellectual disability; Albright hereditary osteodystrophy-like syndrome; Del(2)(q37) 600430 for gene: HDAC4
Publications for gene HDAC4 were changed from 20691407; 15521982; 19365831 to 19365831; 15521982; 20691407; 25402011
Skeletal dysplasia v1.153 NOTCH2 Eleanor Williams Added phenotypes Hajdu-Cheney (Serpentine fibula polycystic kidney) syndrome 102500; Alagille syndrome 2 610205 for gene: NOTCH2
Skeletal dysplasia v1.153 DLL4 Eleanor Williams Added phenotypes Adams-Oliver syndrome 6, 616589 for gene: DLL4
Skeletal dysplasia v1.153 NOTCH1 Eleanor Williams Added phenotypes Limb, scalp and skull defects; AOS; Combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly); Adams-Oliver syndrome 5, 616028 for gene: NOTCH1
Publications for gene NOTCH1 were changed from 25132448; 25963545; 27077170; 25132448 to 25963545; 25132448; 27077170
Skeletal dysplasia v1.153 RBPJ Eleanor Williams Added phenotypes Adams-Oliver syndrome 3, 614814 for gene: RBPJ
Publications for gene RBPJ were changed from 22883147; 28160419 to 28160419; 22883147
Skeletal dysplasia v1.153 DOCK6 Eleanor Williams Added phenotypes Adams-Oliver syndrome 2 614219 for gene: DOCK6
Skeletal dysplasia v1.153 ARHGAP31 Eleanor Williams Added phenotypes Adams-Oliver syndrome 1 100300 for gene: ARHGAP31
Publications for gene ARHGAP31 were changed from 21565291; 29924900 to 29924900; 21565291
Skeletal dysplasia v1.153 EOGT Eleanor Williams Added phenotypes Adams Oliver syndrome 4 for gene: EOGT
Skeletal dysplasia v1.153 FBN1 Eleanor Williams Added phenotypes Geleophysic dysplasia 2 614185; Stiff skin syndrome 184900; Marfan syndrome 154700; Acromicric dysplasia 102370; Weill-Marchesani syndrome 2, dominant 608328 for gene: FBN1
Skeletal dysplasia v1.153 NPR2 Eleanor Williams Added phenotypes Acromesomelic dysplasia, Maroteaux type 602875; Short stature with nonspecific skeletal abnormalities 616255; Epiphyseal chondrodysplasia, Miura type 615923 for gene: NPR2
Skeletal dysplasia v1.153 GDF5 Eleanor Williams Added phenotypes Brachydactyly, type C 113100; Acromesomelic dysplasia, Hunter-Thompson type 201250; Du Pan syndrome 228900; {Osteoarthritis-5} 612400; Chondrodysplasia, Grebe type 200700; Brachydactyly, type A2 112600; Brachydactyly, type A1, C 615072; Symphalangism, proximal, 1B 615298; Multiple synostoses syndrome 2 610017 for gene: GDF5
Skeletal dysplasia v1.153 BMPR1B Eleanor Williams Added phenotypes Brachydactyly, type A1, D 616849; Brachydactyly, type A2 112600; Acromesomelic dysplasia, Demirhan type 609441 for gene: BMPR1B
Skeletal dysplasia v1.153 POLR1A Eleanor Williams Added phenotypes Acrofacial dysostosis, Cincinnati type 616462 for gene: POLR1A
Skeletal dysplasia v1.153 SF3B4 Eleanor Williams Added phenotypes Acrofacial dysostosis 1, Nager type 154400 for gene: SF3B4
Skeletal dysplasia v1.153 PDE4D Eleanor Williams Added phenotypes Acrodysostosis 2, with or without hormone resistance 614613 for gene: PDE4D
Skeletal dysplasia v1.153 PRKAR1A Eleanor Williams Added phenotypes Acrodysostosis 1, with or without hormone resistance 101800 for gene: PRKAR1A
Skeletal dysplasia v1.153 IHH Eleanor Williams Added phenotypes Acrocapitofemoral dysplasia 607778; Brachydactyly, type A1 112500 for gene: IHH
Skeletal dysplasia v1.153 KIF7 Eleanor Williams Added phenotypes Joubert syndrome 12 200990; Acrocallosal syndrome 200990 for gene: KIF7
Skeletal dysplasia v1.153 FGFR3 Eleanor Williams Added phenotypes Thanatophoric dysplasia, type I 187600; Muenke syndrome 602849; CATSHL syndrome 610474; SADDAN 616482; Thanatophoric dysplasia, type II 187601; Achondroplasia 100800; LADD syndrome 149730; Hypochondroplasia 146000; Crouzon syndrome with acanthosis nigricans 612247 for gene: FGFR3
Skeletal dysplasia v1.153 COL2A1 Eleanor Williams Added phenotypes Epiphyseal dysplasia, multiple, with myopia and deafness 132450; Spondyloepiphyseal dysplasia, Stanescu type 616583; Stickler sydrome, type I, nonsyndromic ocular 609508; Achondrogenesis, type II or hypochondrogenesis 200610; Kniest dysplasia 156550; Legg-Calve-Perthes disease 150600; Otospondylomegaepiphyseal dysplasia 215150; Stickler syndrome, type I 108300; SMED Strudwick type 184250; Spondyloperipheral dysplasia 271700; Platyspondylic skeletal dysplasia, Torrance type 151210; Czech dysplasia 609162; SED congenita 183900; Osteoarthritis with mild chondrodysplasia 604864; Avascular necrosis of the femoral head 608805 for gene: COL2A1
Skeletal dysplasia v1.153 TRIP11 Eleanor Williams Added phenotypes Achondrogenesis, type IA 200600 for gene: TRIP11
Skeletal dysplasia v1.153 LMBR1 Eleanor Williams Added phenotypes Laurin-Sandrow syndrome 135750; Polydactyly, preaxial type II 174500; Hypoplastic or aplastic tibia with polydactyly 188740; Triphalangeal thumb, type I 174500; Triphalangeal thumb-polysyndactyly syndrome 174500; Syndactyly, type IV 186200; Acheiropody 200500 for gene: LMBR1
Publications for gene LMBR1 were changed from to 26749485; 11090342
Skeletal dysplasia v1.153 SLC26A2 Eleanor Williams Added phenotypes ACG1B,DD,rMED; multiple epiphyseal dysplasia; Multiple Epiphyseal Dysplasia, Recessive; Epiphyseal dysplasia, multiple, 4 for gene: SLC26A2
Skeletal dysplasia v1.153 SOX9 Eleanor Williams Added phenotypes Campomelic dysplasia with autosomal sex reversal 114290; Acampomelic campomelic dysplasia 114290; Campomelic dysplasia 114290 for gene: SOX9
Skeletal dysplasia v1.153 TWIST2 Eleanor Williams Added phenotypes Ablepharon-macrostomia syndrome 200110; Barber-Say syndrome 209885 for gene: TWIST2
Skeletal dysplasia v1.153 COLEC10 Eleanor Williams Added phenotypes 3MC syndrome 3 -248340 for gene: COLEC10
Publications for gene COLEC10 were changed from to 28301481
Skeletal dysplasia v1.153 COLEC11 Eleanor Williams Added phenotypes 3MC syndrome 2 265050 for gene: COLEC11
Publications for gene COLEC11 were changed from 21258343; 8933348; 2569826 to 21258343; 2569826; 8933348; 28301481
Skeletal dysplasia v1.153 MASP1 Eleanor Williams Added phenotypes 3MC syndrome 1 - 257920 for gene: MASP1
Skeletal dysplasia v1.153 CCDC8 Eleanor Williams Added phenotypes 3-M syndrome 3, 614205 for gene: CCDC8
Skeletal dysplasia v1.153 OBSL1 Eleanor Williams Added phenotypes 3-M syndrome 2 612921 for gene: OBSL1
Skeletal dysplasia v1.153 CUL7 Eleanor Williams Added phenotypes 3-M syndrome 1 273750 for gene: CUL7
Skeletal dysplasia v1.153 FGF9 Eleanor Williams Added phenotypes ?Multiple synostoses syndrome type 3 612961 for gene: FGF9
Skeletal dysplasia v1.153 IFT81 Eleanor Williams Added phenotypes Short-rib thoracic dysplasia 19 with or without polydactyly -617895 for gene: IFT81
Publications for gene IFT81 were changed from 26275418; 28460050; 27666822 to 27666822; 26275418; 28460050
Skeletal dysplasia v1.153 AGPS Eleanor Williams Added phenotypes Rhizomelic chondrodysplasia punctata, type 3 600121 for gene: AGPS
Skeletal dysplasia v1.153 YY1 Eleanor Williams Added phenotypes Gabriele-de Vries syndrome 617557 for gene: YY1
Skeletal dysplasia v1.153 TMEM38B Eleanor Williams Added phenotypes Osteogenesis imperfecta, type XIV 615066; Osteogenesis imperfecta, type XIV, 615066; osteogenesis imperfecta for gene: TMEM38B
Skeletal dysplasia v1.152 TMCO1 Tracy Lester edited their review of gene: TMCO1: Changed rating: GREEN
Skeletal dysplasia v1.152 THPO Tracy Lester edited their review of gene: THPO: Changed rating: RED
Skeletal dysplasia v1.151 FGFR3 Tracy Lester edited their review of gene: FGFR3: Added comment: This gene should definitely be green; Changed rating: GREEN
Skeletal dysplasia v1.151 CEP120 Tracy Lester edited their review of gene: CEP120: Added comment: There are enough cases with specific skeletal phenotype (short rib thoracic dysplasia +/- polydactyly) to call green; Changed rating: GREEN
Skeletal dysplasia v1.151 MANBA Tracy Lester reviewed gene: MANBA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mannosidosis, beta 248510; Mode of inheritance:
Skeletal dysplasia v1.150 MANBA Eleanor Williams reviewed gene: MANBA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.149 MANBA Eleanor Williams gene: MANBA was added
gene: MANBA was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: MANBA was set to
Skeletal dysplasia v1.148 RNU4ATAC Eleanor Williams commented on gene: RNU4ATAC: Initial rating of Amber uploaded on behalf of Tracy Lester was incorrect. She has now corrected this to green.
Skeletal dysplasia v1.148 RNU4ATAC Tracy Lester reviewed gene: RNU4ATAC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type I 210710, Roifman syndrome 616651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.148 RNU4ATAC Tracy Lester Deleted their review
Skeletal dysplasia v1.148 ISCA-37441-Loss Eleanor Williams Source NHS GMS was added to Region: ISCA-37441-Loss.
Skeletal dysplasia v1.148 ISCA-37434-Loss Eleanor Williams Source NHS GMS was added to Region: ISCA-37434-Loss.
Skeletal dysplasia v1.148 ISCA-37418-Loss Eleanor Williams Source NHS GMS was added to Region: ISCA-37418-Loss.
Skeletal dysplasia v1.148 ISCA-37406-Loss Eleanor Williams Source NHS GMS was added to Region: ISCA-37406-Loss.
Skeletal dysplasia v1.148 ISCA-37394-Loss Eleanor Williams Source NHS GMS was added to Region: ISCA-37394-Loss.
Skeletal dysplasia v1.147 ISCA-37441-Loss Eleanor Williams commented on Region: ISCA-37441-Loss
Skeletal dysplasia v1.147 ISCA-37434-Loss Eleanor Williams commented on Region: ISCA-37434-Loss
Skeletal dysplasia v1.147 ISCA-37418-Loss Eleanor Williams commented on Region: ISCA-37418-Loss
Skeletal dysplasia v1.147 ISCA-37406-Loss Eleanor Williams commented on Region: ISCA-37406-Loss
Skeletal dysplasia v1.147 ISCA-37394-Loss Eleanor Williams commented on Region: ISCA-37394-Loss
Skeletal dysplasia v1.147 ZMPSTE24 Tracy Lester reviewed gene: ZMPSTE24: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mandibuloacral dysplasia with type B lipodystrophy 608612, Restrictive dermopathy, lethal 275210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ZIC1 Tracy Lester reviewed gene: ZIC1: Rating: AMBER; Mode of pathogenicity: ; Publications: 26340333; Phenotypes: Craniosynostosis 6 616602; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Skeletal dysplasia v1.147 YY1 Tracy Lester reviewed gene: YY1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28575647; Phenotypes: Gabriele-de Vries syndrome 617557; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 XYLT2 Tracy Lester reviewed gene: XYLT2: Rating: AMBER; Mode of pathogenicity: ; Publications: 26987875; Phenotypes: Spondyloocular syndrome 605822; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 XYLT1 Tracy Lester reviewed gene: XYLT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Desbuquois dysplasia 2 615777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 XRCC4 Tracy Lester reviewed gene: XRCC4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Short stature, microcephaly, and endocrine dysfunction 616541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 WNT7A Tracy Lester reviewed gene: WNT7A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Fuhrmann syndrome 228930, Ulna and fibula, absence of, with severe limb deficiency 276820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 WNT5A Tracy Lester reviewed gene: WNT5A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Robinow syndrome, autosomal dominant 1 180700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 WNT3 Tracy Lester reviewed gene: WNT3: Rating: AMBER; Mode of pathogenicity: ; Publications: 14872406; Phenotypes: Tetra-amelia syndrome 273395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 WNT10B Tracy Lester reviewed gene: WNT10B: Rating: GREEN; Mode of pathogenicity: ; Publications: 24211389; Phenotypes: Split-hand/foot malformation 6 225300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 WNT1 Tracy Lester reviewed gene: WNT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: OI/osteoporosis, Osteogenesis imperfecta, type XV, 615220, {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, 615221, osteogenesis imperfecta; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Skeletal dysplasia v1.147 WISP3 Tracy Lester reviewed gene: WISP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Arthropathy, progressive pseudorheumatoid, of childhood 208230, Spondyloepiphyseal dysplasia tarda with progressive arthropathy 208230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 WDR60 Tracy Lester reviewed gene: WDR60: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Short-rib thoracic dysplasia 8 with or without polydactyly 615503; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 WDR35 Tracy Lester reviewed gene: WDR35: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cranioectodermal dysplasia 2 613610, Short-rib thoracic dysplasia 7 with or without polydactyly 614091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 WDR34 Tracy Lester reviewed gene: WDR34: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Short-rib thoracic dysplasia 11 with or without polydactyly, 615633; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 WDR19 Tracy Lester reviewed gene: WDR19: Rating: AMBER; Mode of pathogenicity: ; Publications: 24504730, 22019273; Phenotypes: Short-rib thoracic dysplasia 5 with or without polydactyly, 614376, Cranioectodermal dysplasia 4, 614378; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 UFSP2 Tracy Lester reviewed gene: UFSP2: Rating: AMBER; Mode of pathogenicity: ; Publications: 28892125, 26428751; Phenotypes: Beukes Hip Dysplasia 142669, Spondyloepimetaphyseal dysplasia, Di Rocco type 617974; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TYROBP Tracy Lester reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Nasu-Hakola disease 221770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TWIST2 Tracy Lester reviewed gene: TWIST2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ablepharon-macrostomia syndrome 200110, Barber-Say syndrome 209885; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TWIST1 Tracy Lester reviewed gene: TWIST1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Craniosynostosis, type 1 123100, Robinow-Sorauf syndrome 180750, Saethre-Chotzen syndrome 101400, Saethre-Chotzen syndrome with eyelid anomalies 101400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 TTC21B Tracy Lester reviewed gene: TTC21B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: SRTD4, Asphyxiating Thoracic Dystrophy, Nephronophthisis 12, 613820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TRPV4 Tracy Lester reviewed gene: TRPV4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Brachyolmia type 3 113500, Digital arthropathy-brachydactyly, familial 606835, Hereditary motor and sensory neuropathy, type IIc 606071, Metatropic dysplasia 156530, Parastremmatic dwarfism 168400, Scapuloperoneal spinal muscular atrophy 181405, SED, Maroteaux type 184095, Spinal muscular atrophy, distal, congenital nonprogressive 600175, Spondylometaphyseal dysplasia, Kozlowski type 184252; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TRPS1 Tracy Lester reviewed gene: TRPS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Trichorhinophalangeal syndrome, type I 190350, Trichorhinophalangeal syndrome, type III 190351; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TRIP11 Tracy Lester reviewed gene: TRIP11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Achondrogenesis, type IA 200600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TREM2 Tracy Lester reviewed gene: TREM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Nasu-Hakola disease 221770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TRAPPC2 Tracy Lester reviewed gene: TRAPPC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondyloepiphyseal dysplasia tarda 313400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v1.147 TP63 Tracy Lester reviewed gene: TP63: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ULT syndrome 103285, Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 604292, Hay-Wells syndrome 106260, Limb-mammary syndrome 603543, Orofacial cleft 8 129400, Rapp-Hodgkin syndrome 129400, Split-hand/foot malformation 4 605289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TNFSF11 Tracy Lester reviewed gene: TNFSF11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 2 259710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TNFRSF11B Tracy Lester reviewed gene: TNFRSF11B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Paget disease of bone 5, juvenile-onset 239000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TNFRSF11A Tracy Lester reviewed gene: TNFRSF11A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteolysis, familial expansile 174810, Osteopetrosis, autosomal recessive 7 612301, Paget disease of bone 2, early-onset 602080; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TMEM67 Tracy Lester reviewed gene: TMEM67: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: COACH syndrome 216360, Joubert syndrome 6 610688, Meckel syndrome 3 607361, {Bardet-Biedl syndrome 14, modifier of} 615991; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TMEM38B Tracy Lester reviewed gene: TMEM38B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteogenesis imperfecta, type XIV 615066, Osteogenesis imperfecta, type XIV, 615066, osteogenesis imperfecta; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TMEM231 Tracy Lester reviewed gene: TMEM231: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Joubert syndrome 20 614970, Meckel syndrome 11 615397; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TMEM216 Tracy Lester reviewed gene: TMEM216: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Joubert syndrome 2 608091, Meckel syndrome 2 603194; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TMEM165 Tracy Lester reviewed gene: TMEM165: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IIk 614727; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TMCO1 Tracy Lester reviewed gene: TMCO1: Rating: RED; Mode of pathogenicity: ; Publications: 24424126; Phenotypes: Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome 213980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 THPO Tracy Lester reviewed gene: THPO: Rating: GREEN; Mode of pathogenicity: ; Publications: 22453305, 19553636; Phenotypes: Thrombocythemia 1 187950 (rare presentation with congenital limb defects); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TGFBR2 Tracy Lester reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Loeys-Dietz syndrome 2 610168; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TGFBR1 Tracy Lester reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Loeys-Dietz syndrome 1 609192; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TGFB2 Tracy Lester reviewed gene: TGFB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Loeys-Dietz syndrome 4 614816; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TGFB1 Tracy Lester reviewed gene: TGFB1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Camurati-Engelmann disease 131300 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TGDS Tracy Lester reviewed gene: TGDS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Catel-Manzke syndrome 616145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TERT Tracy Lester reviewed gene: TERT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Dyskeratosis congenita, autosomal dominant 2 and autosomal recessive 4 613989; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TCTN3 Tracy Lester reviewed gene: TCTN3: Rating: GREEN; Mode of pathogenicity: ; Publications: 22883145; Phenotypes: Joubert syndrome 18 614815, Orofaciodigital syndrome IV 258860; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TCTN2 Tracy Lester reviewed gene: TCTN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Meckel syndrome 8 613885, Joubert syndrome 24 616654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TCTEX1D2 Tracy Lester reviewed gene: TCTEX1D2: Rating: GREEN; Mode of pathogenicity: ; Publications: 26044572, 25830415; Phenotypes: Short-rib thoracic dysplasia 17 with or without polydactyly, 617405 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TCOF1 Tracy Lester reviewed gene: TCOF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Treacher Collins syndrome 1 154500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 TCIRG1 Tracy Lester reviewed gene: TCIRG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 1 259700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TCF12 Tracy Lester reviewed gene: TCF12: Rating: GREEN; Mode of pathogenicity: ; Publications: 23354436; Phenotypes: Craniosynostosis 3 615314; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Skeletal dysplasia v1.147 TBXAS1 Tracy Lester reviewed gene: TBXAS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Ghosal hematodiaphyseal syndrome 231095; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TBX6 Tracy Lester reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylocostal dysostosis 5 122600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TBX5 Tracy Lester reviewed gene: TBX5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Holt-Oram syndrome 142900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TBX4 Tracy Lester reviewed gene: TBX4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Ischiocoxopodopatellar syndrome 147891; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TBX3 Tracy Lester reviewed gene: TBX3: Rating: GREEN; Mode of pathogenicity: ; Publications: 28145909, 30654152, 28961683; Phenotypes: Ulnar-mammary syndrome 181450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 TBX15 Tracy Lester reviewed gene: TBX15: Rating: GREEN; Mode of pathogenicity: ; Publications: 24039145; Phenotypes: Cousin syndrome 260660; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TBCE Tracy Lester reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypoparathyroidism-retardation-dysmorphism syndrome 241410, Kenny-Caffey syndrome, type 1 244460. ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 TALDO1 Tracy Lester reviewed gene: TALDO1: Rating: GREEN; Mode of pathogenicity: ; Publications: 25388407, 26238251; Phenotypes: Transaldolase deficiency 606003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SUMF1 Tracy Lester reviewed gene: SUMF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Multiple sulfatase deficiency 272200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SULF1 Tracy Lester reviewed gene: SULF1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: 20602915; Phenotypes: Mesomelia-synostoses syndrome 600383; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SP7 Tracy Lester reviewed gene: SP7: Rating: AMBER; Mode of pathogenicity: ; Publications: 29382611, 2057926; Phenotypes: Osteogenesis imperfecta, type XII 613849; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SOX9 Tracy Lester reviewed gene: SOX9: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Acampomelic campomelic dysplasia 114290, Campomelic dysplasia 114290, Campomelic dysplasia with autosomal sex reversal 114290; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SOST Tracy Lester reviewed gene: SOST: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Craniodiaphyseal dysplasia, autosomal dominant 122860, Sclerosteosis 1 269500, Van Buchem disease 239100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SNX10 Tracy Lester reviewed gene: SNX10: Rating: GREEN; Mode of pathogenicity: ; Publications: 23280965; Phenotypes: Osteopetrosis, autosomal recessive 8 615085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SNRPB Tracy Lester reviewed gene: SNRPB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cerebrocostomandibular syndrome 117650; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SMOC1 Tracy Lester reviewed gene: SMOC1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21194678, 21194680; Phenotypes: Ophthalmo-acromelic syndrome, Microphthalmia with limb anomalies 206920, Polydactyly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SMC3 Tracy Lester reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cornelia de Lange syndrome 3 610759; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SMC1A Tracy Lester reviewed gene: SMC1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cornelia de Lange syndrome 2 300590; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.147 SMARCAL1 Tracy Lester reviewed gene: SMARCAL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Schimke immunoosseous dysplasia 242900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SMAD4 Tracy Lester reviewed gene: SMAD4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Myhre syndrome 139210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SMAD3 Tracy Lester reviewed gene: SMAD3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Loeys-Dietz syndrome 3 613795; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SLCO5A1 Tracy Lester reviewed gene: SLCO5A1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: 20602915; Phenotypes: Mesomelia-synostoses syndrome 600383; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SLCO2A1 Tracy Lester reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal recessive 2 614441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SLC39A13 Tracy Lester reviewed gene: SLC39A13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylocheirodysplasia, Ehlers-Danlos syndrome-like 612350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SLC35D1 Tracy Lester reviewed gene: SLC35D1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Schneckenbecken dysplasia 269250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SLC34A3 Tracy Lester reviewed gene: SLC34A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypophosphatemic rickets with hypercalciuria 241530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SLC29A3 Tracy Lester reviewed gene: SLC29A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Histiocytosis-lymphadenopathy plus syndrome 602782; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SLC26A2 Tracy Lester reviewed gene: SLC26A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ACG1B,DD,rMED, multiple epiphyseal dysplasia, Multiple Epiphyseal Dysplasia, Recessive, Epiphyseal dysplasia, multiple, 4; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SLC17A5 Tracy Lester reviewed gene: SLC17A5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Sialic acid storage disorder, infantile 269920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SKI Tracy Lester reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Shprintzen-Goldberg syndrome 182212; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SHOX Tracy Lester reviewed gene: SHOX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Langer mesomelic dysplasia 249700, Leri-Weill dyschondrosteosis 127300, Short stature, idiopathic familial 300582; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SH3PXD2B Tracy Lester reviewed gene: SH3PXD2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Frank-ter Haar syndrome 249420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SH3BP2 Tracy Lester reviewed gene: SH3BP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cherubism 118400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SGSH Tracy Lester reviewed gene: SGSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucopolysaccharidisis type IIIA (Sanfilippo A) 252900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SFRP4 Tracy Lester reviewed gene: SFRP4: Rating: GREEN; Mode of pathogenicity: ; Publications: 27355534, 28100910, 27117872, 24096177, 26273529, 22965941, 22387305, 20174869, 27117872; Phenotypes: Pyle disease 265900, PYL, Metaphyseal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SF3B4 Tracy Lester reviewed gene: SF3B4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Acrofacial dysostosis 1, Nager type 154400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SETD2 Tracy Lester reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Luscan-Lumish syndrome 616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SERPINH1 Tracy Lester reviewed gene: SERPINH1: Rating: AMBER; Mode of pathogenicity: ; Publications: 20188343, 25510505; Phenotypes: OI3, {Preterm premature rupture of the membranes, susceptibility to}, 610504, Osteogenesis imperfecta, type X, 613848, Osteogenesis Imperfecta, Recessive, Osteogenesis Imperfecta and Decreased Bone Density, skeletal dysplasias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SERPINF1 Tracy Lester reviewed gene: SERPINF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: OI/osteoporosis, Osteogenesis imperfecta, type VI, 613982, Osteogenesis Imperfecta, Recessive, osteogenesis imperfecta; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SEC24D Tracy Lester reviewed gene: SEC24D: Rating: GREEN; Mode of pathogenicity: ; Publications: 25683121; Phenotypes: Cole-Carpenter syndrome, Osteogenesis Imperfecta, Cole Carpenter syndrome, SYNDROMIC OSTEOGENESIS IMPERFECTA; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SCARF2 Tracy Lester reviewed gene: SCARF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Van den Ende-Gupta syndrome 600920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SBDS Tracy Lester reviewed gene: SBDS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Shwachman-Diamond syndrome 260400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 SALL4 Tracy Lester reviewed gene: SALL4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Okihiro (Duane-radial ray) syndrome 607323, IVIC syndrome 147750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 SALL1 Tracy Lester reviewed gene: SALL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Townes Brocks syndrome (Renal-Ear-Anal-Radial syndrome) 107480; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 RUNX2 Tracy Lester reviewed gene: RUNX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cleidocranial dysplasia 119600, Cleidocranial dysplasia, forme fruste, dental anomalies only 119600, Cleidocranial dysplasia, forme fruste, with brachydactyly 119600, Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 156510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 RPGRIP1L Tracy Lester reviewed gene: RPGRIP1L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: COACH syndrome 216360, Joubert syndrome 7 611560, Meckel syndrome 5 611561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ROR2 Tracy Lester reviewed gene: ROR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Brachydactyly, type B1 113000, Robinow syndrome, autosomal recessive 268310; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 RNU4ATAC Tracy Lester reviewed gene: RNU4ATAC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type I 210710, Roifman syndrome 616651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 RMRP Tracy Lester reviewed gene: RMRP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Anauxetic dysplasia 607095, Cartilage-hair hypoplasia 250250, Metaphyseal dysplasia without hypotrichosis 250460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 RIPPLY2 Tracy Lester reviewed gene: RIPPLY2: Rating: AMBER; Mode of pathogenicity: ; Publications: 26238661, 25343988; Phenotypes: Spondylocostal dysostosis 6 - 616566; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 RFT1 Tracy Lester reviewed gene: RFT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital disorder of glycosylation, type In 612015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 RECQL4 Tracy Lester reviewed gene: RECQL4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Baller-Gerold syndrome 218600, RAPILINO syndrome 266280, Rothmund-Thomson syndrome 268400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 WRN Tracy Lester reviewed gene: WRN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Werner syndrome -277700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 RBPJ Tracy Lester reviewed gene: RBPJ: Rating: AMBER; Mode of pathogenicity: ; Publications: 22883147, 28160419; Phenotypes: Adams-Oliver syndrome 3, 614814; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 RBM8A Tracy Lester reviewed gene: RBM8A: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Thrombocytopenia-absent radius syndrome 274000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 RASGRP2 Tracy Lester reviewed gene: RASGRP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 18709451, 24958846; Phenotypes: Bleeding disorder, platelet-type, 18 615888; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 RAD21 Tracy Lester reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cornelia de Lange syndrome 4 614701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 RAB33B Tracy Lester reviewed gene: RAB33B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Smith-McCort dysplasia 2 615222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 RAB23 Tracy Lester reviewed gene: RAB23: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Carpenter syndrome 201000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 PYCR1 Tracy Lester reviewed gene: PYCR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cutis laxa, autosomal recessive, type IIB 612940, Cutis laxa, autosomal recessive, type IIIB 614438; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PUF60 Tracy Lester reviewed gene: PUF60: Rating: GREEN; Mode of pathogenicity: ; Publications: 28327570, 27804958, 24140112; Phenotypes: Verheij syndrome, 615583, VRJS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 PTPN11 Tracy Lester reviewed gene: PTPN11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: LEOPARD syndrome 1 151100, Metachondromatosis 156250, Noonan syndrome 1 163950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 PTHLH Tracy Lester reviewed gene: PTHLH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Brachydactyly, type E2 613382; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 PTH1R Tracy Lester reviewed gene: PTH1R: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Chondrodysplasia, Blomstrand type 215045, Eiken syndrome 600002, Failure of tooth eruption, primary 125350, Metaphyseal chondrodysplasia, Murk Jansen type 156400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PTDSS1 Tracy Lester reviewed gene: PTDSS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Lenz-Majewski hyperostotic dwarfism 151050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 PSPH Tracy Lester reviewed gene: PSPH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Phosphoserine phosphatase deficiency 614023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PSAT1 Tracy Lester reviewed gene: PSAT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Neu-Laxova syndrome 2 616038; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PRMT7 Tracy Lester reviewed gene: PRMT7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Short stature, brachydactyly, intellectual developmental disability, and seizures 617157; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PRKAR1A Tracy Lester reviewed gene: PRKAR1A: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Acrodysostosis 1, with or without hormone resistance 101800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PPIB Tracy Lester reviewed gene: PPIB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteogenesis imperfecta, type IX 259440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 POR Tracy Lester reviewed gene: POR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750, Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 POP1 Tracy Lester reviewed gene: POP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21455487, 27380734, 28067412; Phenotypes: Anauxetic dysplasia 2, 617396; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 POLR1D Tracy Lester reviewed gene: POLR1D: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Treacher Collins syndrome 2 613717; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 POLR1C Tracy Lester reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Treacher Collins syndrome 3 248390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 POLR1A Tracy Lester reviewed gene: POLR1A: Rating: GREEN; Mode of pathogenicity: ; Publications: 25913037; Phenotypes: Acrofacial dysostosis, Cincinnati type 616462; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 POC1A Tracy Lester reviewed gene: POC1A: Rating: GREEN; Mode of pathogenicity: ; Publications: 26162852, 26336158, 26374189; Phenotypes: Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis 614813; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PLS3 Tracy Lester reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Bone mineral density QTL18, osteoporosis 300910; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.147 PLOD2 Tracy Lester reviewed gene: PLOD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Bruck syndrome 2 609220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PLEKHM1 Tracy Lester reviewed gene: PLEKHM1: Rating: AMBER; Mode of pathogenicity: ; Publications: 27291868, 17997709, 17404618; Phenotypes: Osteopetrosis, autosomal recessive 6 - 611497, Osteopetrosis, autosomal dominant 3 - 618107; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PITX1 Tracy Lester reviewed gene: PITX1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23587911, 23022097, 30459804; Phenotypes: Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 119800, Liebenberg syndrome 186550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 PIK3R1 Tracy Lester reviewed gene: PIK3R1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: SHORT syndrome 269880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 PIK3CA Tracy Lester reviewed gene: PIK3CA: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: CLOVES 612918; Mode of inheritance: Mosaicism
Skeletal dysplasia v1.147 PIGV Tracy Lester reviewed gene: PIGV: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyperphosphatasia with mental retardation syndrome 1 239300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PIGT Tracy Lester reviewed gene: PIGT: Rating: GREEN; Mode of pathogenicity: ; Publications: 28327575, 29868109; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 3 615398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PHGDH Tracy Lester reviewed gene: PHGDH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Neu-Laxova syndrome 1 256520, Phosphoglycerate dehydrogenase deficiency 601815; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PHEX Tracy Lester reviewed gene: PHEX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypophosphatemic rickets, X-linked dominant 307800; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.147 PGM3 Tracy Lester reviewed gene: PGM3: Rating: AMBER; Mode of pathogenicity: ; Publications: 24931394; Phenotypes: Immunodeficiency 23 615816; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PEX7 Tracy Lester reviewed gene: PEX7: Rating: GREEN; Mode of pathogenicity: ; Publications: 7719337, 28742517, 25800479 ; Phenotypes: Rhizomelic CDP type 1, Rhizomelic chondrodysplasia punctata, type 1, 215100 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PEX5 Tracy Lester reviewed gene: PEX5: Rating: GREEN; Mode of pathogenicity: ; Publications: 18712838; Phenotypes: Peroxisome biogenesis disorder 2A (Zellweger) 214110, Rhizomelic chondrodysplasia punctata, type 5 616716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PDE4D Tracy Lester reviewed gene: PDE4D: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Acrodysostosis 2, with or without hormone resistance 614613; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 PDE3A Tracy Lester reviewed gene: PDE3A: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 25961942, 9696728; Phenotypes: Hypertension and brachydactyly syndrome, 112410; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 PCYT1A Tracy Lester reviewed gene: PCYT1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylometaphyseal dysplasia with cone-rod dystrophy 608940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PCNT Tracy Lester reviewed gene: PCNT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type II 210720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PAPSS2 Tracy Lester reviewed gene: PAPSS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Brachyolmia 4 with mild epiphyseal and metaphyseal changes 612847; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 PAM16 Tracy Lester reviewed gene: PAM16: Rating: GREEN; Mode of pathogenicity: ; Publications: 27354339, 24786642; Phenotypes: Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type 613320; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 P4HB Tracy Lester reviewed gene: P4HB: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 25683117, 29384951, 30063094; Phenotypes: Cole-Carpenter syndrome 1 112240; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 P3H1 Tracy Lester reviewed gene: P3H1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteogenesis imperfecta, type VIII 610915; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 OSTM1 Tracy Lester reviewed gene: OSTM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 5 259720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ORC6 Tracy Lester reviewed gene: ORC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Meier-Gorlin syndrome 3 613803; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ORC4 Tracy Lester reviewed gene: ORC4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Meier-Gorlin syndrome 2 613800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ORC1 Tracy Lester reviewed gene: ORC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Meier-Gorlin syndrome 1 224690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 OFD1 Tracy Lester reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Joubert syndrome 10 300804, Orofaciodigital syndrome I 311200 XLD, Simpson-Golabi-Behmel syndrome, type 2 300209 XLR; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.147 OBSL1 Tracy Lester reviewed gene: OBSL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: 3-M syndrome 2 612921; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 OAT Tracy Lester reviewed gene: OAT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Gyrate atrophy of choroid and retina with or without ornithinemia 258870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 NSDHL Tracy Lester reviewed gene: NSDHL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital hemidysplasia, ichthyosis, limb defects (CHILD) syndrome 308050, CK syndrome 300831; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.147 NSD1 Tracy Lester reviewed gene: NSD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Sotos syndrome 1 117550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 NPR2 Tracy Lester reviewed gene: NPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Acromesomelic dysplasia, Maroteaux type 602875, Epiphyseal chondrodysplasia, Miura type 615923, Short stature with nonspecific skeletal abnormalities 616255; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 NOTCH2 Tracy Lester reviewed gene: NOTCH2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Alagille syndrome 2 610205, Hajdu-Cheney (Serpentine fibula polycystic kidney) syndrome 102500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 NOTCH1 Tracy Lester reviewed gene: NOTCH1: Rating: GREEN; Mode of pathogenicity: ; Publications: 25132448, 25963545, 27077170, 25132448; Phenotypes: Adams-Oliver syndrome 5, 616028, Combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly), AOS, Limb, scalp and skull defects; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v1.147 NOG Tracy Lester reviewed gene: NOG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Brachydactyly, type B2 611377, Multiple synostoses syndrome 1 186500, Stapes ankylosis with broad thumb and toes 184460, Symphalangism, proximal, 1A 185800, Tarsal-carpal coalition syndrome 186570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 NLRP3 Tracy Lester reviewed gene: NLRP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Chronic infantile neurologic cutaneous articular syndrome (CINA) - 607115; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 NKX3-2 Tracy Lester reviewed gene: NKX3-2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylo-megaepiphyseal-metaphyseal dysplasia 613330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 NIPBL Tracy Lester reviewed gene: NIPBL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cornelia de Lange syndrome 1 122470; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 NIN Tracy Lester reviewed gene: NIN: Rating: AMBER; Mode of pathogenicity: ; Publications: 22933543, 23665482; Phenotypes: Seckel syndrome 7 614851; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 NFIX Tracy Lester reviewed gene: NFIX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Marshall-Smith syndrome 602535, Sotos syndrome 2 614753; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 NF1 Tracy Lester reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Neurofibromatosis, familial spinal 162210, Neurofibromatosis, type 1 162200, Neurofibromatosis-Noonan syndrome 601321; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 NEU1 Tracy Lester reviewed gene: NEU1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Sialidosis, type I 256550, Sialidosis, type II 256550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 NEK1 Tracy Lester reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Short rib thoracic dysplasia 6 with or without polydactyly - 263520; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 NANS Tracy Lester reviewed gene: NANS: Rating: GREEN; Mode of pathogenicity: ; Publications: 27213289; Phenotypes: Spondyloepimetaphyseal dysplasia, Camera-Genevieve type 610442 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 NAGLU Tracy Lester reviewed gene: NAGLU: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucopolysaccharidosis type IIIB (Sanfilippo B) 252920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MYCN Tracy Lester reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Feingold syndrome (Microcephaly-oculo-digito-esophageal-duodenal) 164280; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 MSX2 Tracy Lester reviewed gene: MSX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Craniosynostosis, type 2 604757, Parietal foramina 1 168500, Parietal foramina with cleidocranial dysplasia 168550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 MPDU1 Tracy Lester reviewed gene: MPDU1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital disorder of glycosylation, type If 609180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MNX1 Tracy Lester reviewed gene: MNX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Currarino syndrome 176450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 MMP9 Tracy Lester reviewed gene: MMP9: Rating: GREEN; Mode of pathogenicity: ; Publications: 19615667, 28342220, 24781753; Phenotypes: Metaphyseal anadysplasia 2 613073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MMP2 Tracy Lester reviewed gene: MMP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Multicentric osteolysis, nodulosis, and arthropathy 259600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MMP13 Tracy Lester reviewed gene: MMP13: Rating: GREEN; Mode of pathogenicity: ; Publications: 24648384; Phenotypes: Metaphyseal anadysplasia 1 602111, Spondyloepimetaphyseal dysplasia, Missouri type 602111, Metaphyseal dysplasia, Spahr type - 250400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MKS1 Tracy Lester reviewed gene: MKS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome 13 615990, Meckel syndrome 1 249000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MIR17HG Tracy Lester reviewed gene: MIR17HG: Rating: RED; Mode of pathogenicity: ; Publications: 21892160, 25391829, 19344873, 26360630; Phenotypes: Feingold syndrome 2, 614326; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 MGP Tracy Lester reviewed gene: MGP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Keutel syndrome 245150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MESP2 Tracy Lester reviewed gene: MESP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 15122512, 18485326; Phenotypes: Spondylocostal dysostosis 2, autosomal recessive 608681; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MEOX1 Tracy Lester reviewed gene: MEOX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Klippel-Feil syndrome 2 214300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MEGF8 Tracy Lester reviewed gene: MEGF8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Carpenter syndrome 2 614976; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MATN3 Tracy Lester reviewed gene: MATN3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Epiphyseal dysplasia, multiple, 5, 607078, Spondyloepimetaphyseal dysplasia, 608728; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 MASP1 Tracy Lester reviewed gene: MASP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: 3MC syndrome 1 - 257920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MAP3K7 Tracy Lester reviewed gene: MAP3K7: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 27426733; Phenotypes: Frontometaphyseal dysplasia 2, 617137; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v1.147 MAN2B1 Tracy Lester reviewed gene: MAN2B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mannosidosis, alpha-, types I and II 248500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MAFB Tracy Lester reviewed gene: MAFB: Rating: GREEN; Mode of pathogenicity: ; Publications: 2387013, 30305815, 30430035; Phenotypes: Multicentric carpotarsal osteolysis syndrome 166300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 LTBP3 Tracy Lester reviewed gene: LTBP3: Rating: GREEN; Mode of pathogenicity: ; Publications: 27068007; Phenotypes: Geleophysic dysplasia 3 617809, Dental anomalies and short stature 610216; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v1.147 LTBP2 Tracy Lester reviewed gene: LTBP2: Rating: AMBER; Mode of pathogenicity: ; Publications: 22539340; Phenotypes: Weill-Marchesani; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 LRP5 Tracy Lester reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyperostosis, endosteal 144750, Osteopetrosis, autosomal dominant 1 607634, Osteoporosis-pseudoglioma syndrome 259770, Osteosclerosis 144750, van Buchem disease, type 2 607636, [Bone mineral density variability 1] 601884, {Osteoporosis} 166710; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Skeletal dysplasia v1.147 LRP4 Tracy Lester reviewed gene: LRP4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cenani-Lenz syndactyly syndrome 212780, Sclerosteosis 2 614305; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 LPIN2 Tracy Lester reviewed gene: LPIN2: Rating: GREEN; Mode of pathogenicity: ; Publications: 29912021; Phenotypes: Majeed syndrome (Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia) 609628; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 LONP1 Tracy Lester reviewed gene: LONP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: CODAS (Cerebral, Ocular, Dental, Auricular and Skeletal anomalies) syndrome 600373; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 LMX1B Tracy Lester reviewed gene: LMX1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Nail-patella syndrome 161200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 LMNA Tracy Lester reviewed gene: LMNA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mandibuloacral dysplasia 248370, 616516, Heart-hand syndrome, Slovenian type 610140, Hutchinson-Gilford progeria 176670; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 LMBR1 Tracy Lester reviewed gene: LMBR1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 26749485, 11090342; Phenotypes: Acheiropody 200500, Hypoplastic or aplastic tibia with polydactyly 188740, Laurin-Sandrow syndrome 135750, Polydactyly, preaxial type II 174500, Syndactyly, type IV 186200, Triphalangeal thumb, type I 174500, Triphalangeal thumb-polysyndactyly syndrome 174500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 LIFR Tracy Lester reviewed gene: LIFR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome 601559; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 LFNG Tracy Lester reviewed gene: LFNG: Rating: AMBER; Mode of pathogenicity: ; Publications: 16385447, 30196550; Phenotypes: Spondylocostal dysostosis 3, autosomal recessive 609813; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 LEMD3 Tracy Lester reviewed gene: LEMD3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Buschke-Ollendorff syndrome 166700, Melorheostosis with osteopoikilosis 155950 IC, Osteopoikilosis 166700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 LBR Tracy Lester reviewed gene: LBR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Greenberg skeletal dysplasia 215140, Pelger-Huet anomaly 169400, Pelger-Huet anomaly with mild skeletal anomalies 618019; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 KMT2D Tracy Lester reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Kabuki syndrome 1 - 147920; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 KIF7 Tracy Lester reviewed gene: KIF7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Acrocallosal syndrome 200990, Joubert syndrome 12 200990; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 KIF22 Tracy Lester reviewed gene: KIF22: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondyloepimetaphyseal dysplasia with joint laxity, type 2 603546; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 KAT6B Tracy Lester reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Genitopatellar syndrome 606170, SBBYSS syndrome 603736; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 KAT6A Tracy Lester reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mental retardation, autosomal dominant 32 - 616268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 INPPL1 Tracy Lester reviewed gene: INPPL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Opsismodysplasia 258480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IMPAD1 Tracy Lester reviewed gene: IMPAD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Chondrodysplasia with joint dislocations, GPAPP type 614078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IL1RN Tracy Lester reviewed gene: IL1RN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Interleukin 1 receptor antagonist deficiency 612852; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IL11RA Tracy Lester reviewed gene: IL11RA: Rating: GREEN; Mode of pathogenicity: ; Publications: 21741611; Phenotypes: Craniosynostosis and dental anomalies 614188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 IKBKG Tracy Lester reviewed gene: IKBKG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency 300301, Incontinentia pigmenti 308300; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.147 IHH Tracy Lester reviewed gene: IHH: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Acrocapitofemoral dysplasia 607778, Brachydactyly, type A1 112500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IGF1R Tracy Lester reviewed gene: IGF1R: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IFT81 Tracy Lester reviewed gene: IFT81: Rating: AMBER; Mode of pathogenicity: ; Publications: 26275418, 28460050, 27666822; Phenotypes: Short-rib thoracic dysplasia 19 with or without polydactyly -617895; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IFT80 Tracy Lester reviewed gene: IFT80: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Short-rib thoracic dysplasia 2 with or without polydactyly 611263; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IFT52 Tracy Lester reviewed gene: IFT52: Rating: AMBER; Mode of pathogenicity: ; Publications: 2688018, 27466190; Phenotypes: SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY, SRTD16 #617102; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IFT43 Tracy Lester reviewed gene: IFT43: Rating: AMBER; Mode of pathogenicity: ; Publications: 21378380, 22791528, 26892345, 24027799, 28400947; Phenotypes: Short-rib thoracic dysplasia 18 with polydactyly - 617866, ?Cranioectodermal dysplasia 3 - 614099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IFT172 Tracy Lester reviewed gene: IFT172: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: SRTD10, Short-rib thoracic dysplasia 10 with or without polydactyly, 615630; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IFT140 Tracy Lester reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Short-rib thoracic dysplasia 9 with of without polydactyly, 266920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IFT122 Tracy Lester reviewed gene: IFT122: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cranioectodermal dysplasia 1 218330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IFITM5 Tracy Lester reviewed gene: IFITM5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteogenesis imperfecta, type V 610967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 IFIH1 Tracy Lester reviewed gene: IFIH1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 25620204; Phenotypes: Singleton-Merten syndrome 1 (182250); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 IDUA Tracy Lester reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucopolysaccharidosis Ih 607014, Mucopolysaccharidosis Ih/s 607015, Mucopolysaccharidosis Is 607016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 IDS Tracy Lester reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucopolysaccharidosis II 309900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v1.147 IDH2 Tracy Lester reviewed gene: IDH2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 22057236, 22057234, 24049096; Phenotypes: Enchondromatosis (Ollier) and Enchondromatosis with hermangiomata (Maffucci) 166000, metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (614875); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 IDH1 Tracy Lester reviewed gene: IDH1: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: 22025298, 22057236, 22057234, 24049096; Phenotypes: Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria 614875, Maffucci syndrome 614569, Ollier disease/ Dyschondroplasia 166000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 ICK Tracy Lester reviewed gene: ICK: Rating: AMBER; Mode of pathogenicity: ; Publications: 27069622, 19185282; Phenotypes: Endocrine-cerebroosteodysplasia 612651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 HSPG2 Tracy Lester reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Dyssegmental dysplasia, Silverman-Handmaker type 224410, Schwartz-Jampel syndrome, type 1 255800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 HNRNPK Tracy Lester reviewed gene: HNRNPK: Rating: AMBER; Mode of pathogenicity: ; Publications: 26173930, 26954065, 26638989; Phenotypes: Au-Kline syndrome:616580, Orphanet:453499; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 HPGD Tracy Lester reviewed gene: HPGD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cranioosteoarthropathy 259100, Digital clubbing, isolated congenital 119900, Hypertrophic osteoarthropathy, primary, autosomal recessive 1 259100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 HOXD13 Tracy Lester reviewed gene: HOXD13: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 9758628, 12649808, 17236141; Phenotypes: Brachydactyly-syndactyly syndrome 610713, Brachydactyly, type D 113200, Brachydactyly, type E 113300, Syndactyly, type V 186300, Synpolydactyly 1 186000 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 HOXD11 Tracy Lester reviewed gene: HOXD11: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: Fleischman 2013 Blood 122:4837 http://www.bloodjournal.org/content/122/21/4837 (not in PubMed); Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 HOXA13 Tracy Lester reviewed gene: HOXA13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Guttmacher syndrome 176305, Hand-foot-uterus syndrome 140000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 HOXA11 Tracy Lester reviewed gene: HOXA11: Rating: AMBER; Mode of pathogenicity: ; Publications: 11101832; Phenotypes: Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 605432; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 HGSNAT Tracy Lester reviewed gene: HGSNAT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucopolysaccharidosis type IIIC (Sanfilippo C) 252930; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 HES7 Tracy Lester reviewed gene: HES7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylocostal dysostosis 4, autosomal recessive 613686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 HDAC8 Tracy Lester reviewed gene: HDAC8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cornelia de Lange syndrome 5 300882, Wilson-Turner syndrome 309585; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.147 HDAC4 Tracy Lester reviewed gene: HDAC4: Rating: AMBER; Mode of pathogenicity: ; Publications: 20691407, 15521982, 19365831, 25402011; Phenotypes: Albright hereditary osteodystrophy type 3, Albright hereditary osteodystrophy-like syndrome, Brachydactyly-intellectual disability, Del(2)(q37) 600430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 GZF1 Tracy Lester reviewed gene: GZF1: Rating: AMBER; Mode of pathogenicity: ; Publications: 28475863; Phenotypes: Larsen syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GUSB Tracy Lester reviewed gene: GUSB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucopolysaccharidosis VII 253220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GSC Tracy Lester reviewed gene: GSC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Foundation Trust) Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities 602471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GPX4 Tracy Lester reviewed gene: GPX4: Rating: AMBER; Mode of pathogenicity: ; Publications: 24706940; Phenotypes: Spondylometaphyseal dysplasia, Sedaghatian type 250220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GPC6 Tracy Lester reviewed gene: GPC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Omodysplasia 1 258315; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GORAB Tracy Lester reviewed gene: GORAB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Geroderma osteodysplasticum 231070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GNS Tracy Lester reviewed gene: GNS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucopolysaccharidosis type IIID 252940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GNPTG Tracy Lester reviewed gene: GNPTG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucolipidosis III gamma 252605; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GNPTAB Tracy Lester reviewed gene: GNPTAB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucolipidosis II alpha/beta 252500, Mucolipidosis III alpha/beta 252600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GNPAT Tracy Lester reviewed gene: GNPAT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: RCDP2, Rhizomelic Chondrodysplasia Punctata, Chondrodysplasia punctata, rhizomelic, type 2, 222765, Rhizomelic chondrodysplasia punctata type 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GNAS Tracy Lester reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: McCune-Albright syndrome, somatic, mosaic 174800, Osseous heteroplasia, progressive 166350, Pseudohypoparathyroidism Ia 103580, Pseudohypoparathyroidism Ib 603233; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Skeletal dysplasia v1.147 GLI3 Tracy Lester reviewed gene: GLI3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Greig cephalopolysyndactyly syndrome 175700, Pallister-Hall syndrome 146510, Polydactyly, postaxial, types A1 and B 174200, Polydactyly, preaxial, type IV 174700, {Hypothalamic hamartomas, somatic} 241800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 GLB1 Tracy Lester reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: GM1-gangliosidosis, type I 230500, Mucopolysaccharidosis type IVB (Morquio) 253010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GJA1 Tracy Lester reviewed gene: GJA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Craniometaphyseal dysplasia, autosomal recessive 218400, Erythrokeratodermia variabilis et progressiva 133200, Hypoplastic left heart syndrome 1 241550, Oculodentodigital dysplasia 164200, Oculodentodigital dysplasia, autosomal recessive 257850, Palmoplantar keratoderma with congenital alopecia 104100, Syndactyly, type III 186100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GHR Tracy Lester reviewed gene: GHR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Laron dwarfism, 262500, Growth hormone insensitivity, increased responsiveness to growth hormone 604271; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GDF6 Tracy Lester reviewed gene: GDF6: Rating: GREEN; Mode of pathogenicity: ; Publications: 18425797; Phenotypes: Klippel-Feil syndrome 1, autosomal dominant 118100, Multiple synostoses syndrome type 4 - 617898.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 GDF5 Tracy Lester reviewed gene: GDF5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Acromesomelic dysplasia, Hunter-Thompson type 201250, Brachydactyly, type A1, C 615072, Brachydactyly, type A2 112600, Brachydactyly, type C 113100, Chondrodysplasia, Grebe type 200700, Du Pan syndrome 228900, Multiple synostoses syndrome 2 610017, Symphalangism, proximal, 1B 615298, {Osteoarthritis-5} 612400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 GDF3 Tracy Lester reviewed gene: GDF3: Rating: AMBER; Mode of pathogenicity: ; Publications: 19864492; Phenotypes: Klippel-Feil anomaly with laryngeal malformation - 613702; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 GALNT3 Tracy Lester reviewed gene: GALNT3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Tumoral calcinosis, hyperphosphatemic, familial I 211900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 GALNS Tracy Lester reviewed gene: GALNS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucopolysaccharidosis IVA 253000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 FZD2 Tracy Lester reviewed gene: FZD2: Rating: GREEN; Mode of pathogenicity: ; Publications: 25759469, 29230162, 29383830, 29383834, 30455931; Phenotypes: Autosomal dominant omodysplasia type 2 164745; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 FUCA1 Tracy Lester reviewed gene: FUCA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Fucosidosis 230000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 FN1 Tracy Lester reviewed gene: FN1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 29100092; Phenotypes: Spondylometaphyseal dysplasia, corner fracture type 184255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 FLNB Tracy Lester reviewed gene: FLNB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Atelosteogenesis, type I 108720, Atelosteogenesis, type III 108721, Boomerang dysplasia 112310, Larsen syndrome 150250, Spondylocarpotarsal synostosis syndrome 272460; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 FLNA Tracy Lester reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Melnick Needles syndrome 309350, Otopalatodigital syndrome, type I -311300, Otopalatodigital syndrome, type II -304120, Frontometaphyseal dysplasia 305620, Terminal osseous dysplasia 300244; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Skeletal dysplasia v1.147 FKBP10 Tracy Lester reviewed gene: FKBP10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Brucks syndrome 1 - 259450, Osteogenesis imperfecta, type XI, 610968; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 FIG4 Tracy Lester reviewed gene: FIG4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Yunis-Varon syndrome 216340; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 FGFR3 Tracy Lester reviewed gene: FGFR3: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Achondroplasia 100800, CATSHL syndrome 610474, Crouzon syndrome with acanthosis nigricans 612247, Hypochondroplasia 146000, LADD syndrome 149730, Muenke syndrome 602849, SADDAN 616482, Thanatophoric dysplasia, type I 187600, Thanatophoric dysplasia, type II 187601; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 FGFR2 Tracy Lester reviewed gene: FGFR2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 207410, Apert syndrome 101200, Beare-Stevenson cutis gyrata syndrome 123790, Bent bone dysplasia syndrome 614592, Craniofacial-skeletal-dermatologic dysplasia 101600, Craniosynostosis, nonspecific Crouzon syndrome 123500, Gastric cancer, somatic 613659, Jackson-Weiss syndrome 123150, LADD syndrome 149730, Pfeiffer syndrome 101600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 FGFR1 Tracy Lester reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Hartsfield syndrome 615465, Jackson-Weiss syndrome 123150, Osteoglophonic dysplasia 166250, Pfeiffer syndrome 101600, Trigonocephaly 1 190440; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 FGF23 Tracy Lester reviewed gene: FGF23: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypophosphatemic rickets, autosomal dominant 193100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 FGF16 Tracy Lester reviewed gene: FGF16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Metacarpal 4-5 fusion 309630; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v1.147 FGF10 Tracy Lester reviewed gene: FGF10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: LADD syndrome 149730; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 FGF9 Tracy Lester reviewed gene: FGF9: Rating: AMBER; Mode of pathogenicity: ; Publications: 19589401; Phenotypes: ?Multiple synostoses syndrome type 3 612961; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 FERMT3 Tracy Lester reviewed gene: FERMT3: Rating: GREEN; Mode of pathogenicity: ; Publications: 18709451; Phenotypes: Leukocyte adhesion deficiency, type III 612840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 FBN2 Tracy Lester reviewed gene: FBN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Contractural arachnodactyly, congenital 121050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 FBN1 Tracy Lester reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Acromicric dysplasia 102370, Geleophysic dysplasia 2 614185, Marfan syndrome 154700, Stiff skin syndrome 184900, Weill-Marchesani syndrome 2, dominant 608328; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 FBLN1 Tracy Lester reviewed gene: FBLN1: Rating: AMBER; Mode of pathogenicity: ; Publications: 24084572; Phenotypes: Synpolydactyly, 3/3'4, associated with metacarpal and metatarsal synostoses 608180; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 FBLIM1 Tracy Lester reviewed gene: FBLIM1: Rating: AMBER; Mode of pathogenicity: ; Publications: 29912021; Phenotypes: Majeed syndrome (Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia) 609628; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 FAM58A Tracy Lester reviewed gene: FAM58A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: STAR syndrome 300707; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.147 FAM20C Tracy Lester reviewed gene: FAM20C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Raine syndrome 259775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 FAM111A Tracy Lester reviewed gene: FAM111A: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Gracile bone dysplasia 602361, Kenny-Caffey syndrome, type 2 127000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 EZH2 Tracy Lester reviewed gene: EZH2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Weaver syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 EXTL3 Tracy Lester reviewed gene: EXTL3: Rating: GREEN; Mode of pathogenicity: ; Publications: 28148688, 28132690; Phenotypes: Immunoskeletal dysplasia with neurodevelopmental abnormalities 617425; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 EXT2 Tracy Lester reviewed gene: EXT2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Exostoses, multiple, type 2 133701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 EXT1 Tracy Lester reviewed gene: EXT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Exostoses, multiple, type 13370, trichorhinophalangeal syndrome type 2 -150230; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 EVC2 Tracy Lester reviewed gene: EVC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Ellis-van Creveld syndrome 225500, Weyers acrofacial dysostosis 193530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 EVC Tracy Lester reviewed gene: EVC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ECV1, Ellis-van Creveld syndrome, 225500, ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ESCO2 Tracy Lester reviewed gene: ESCO2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Roberts syndrome 268300, SC phocomelia syndrome 269000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ERF Tracy Lester reviewed gene: ERF: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 23354439, 26097063; Phenotypes: Craniosynostosis 4 600775, Chitayat syndrome - 617180; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 EP300 Tracy Lester reviewed gene: EP300: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Rubinstein-Taybi syndrome 180849; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 EOGT Tracy Lester reviewed gene: EOGT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Adams Oliver syndrome 4; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ENPP1 Tracy Lester reviewed gene: ENPP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cole disease 615522, Hypophosphatemic rickets, autosomal recessive, 2 613312; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 EIF2AK3 Tracy Lester reviewed gene: EIF2AK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Wolcott-Rallison syndrome 226980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 EFTUD2 Tracy Lester reviewed gene: EFTUD2: Rating: GREEN; Mode of pathogenicity: ; Publications: 19334086, 16760738, 22305528; Phenotypes: Mandibulofacial dysostosis, Guion-Almeida type 610536; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 EFNB1 Tracy Lester reviewed gene: EFNB1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Craniofrontonasal dysplasia 304110; Mode of inheritance: X-LINKED: hemizygous mutation in males is generally not pathogenic, monoallelic mutations in females may cause disease, as do mosaic mutations in males ; Current diagnostic: yes
Skeletal dysplasia v1.147 EED Tracy Lester reviewed gene: EED: Rating: GREEN; Mode of pathogenicity: ; Publications: 25787343, 27193220, 27868325, 28229514; Phenotypes: Cohen-Gibson syndrome 617561; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 EBP Tracy Lester reviewed gene: EBP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: CDPXLD, Chondrodysplasia punctata, X-linked dominant, 302960, MEND syndrome-300960 XLR.; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.147 DYNC2LI1 Tracy Lester reviewed gene: DYNC2LI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: SHORT-RIB THORACIC DYSPLASIA 15 WITH POLYDACTYLY, SRTD15 #617088; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DYNC2H1 Tracy Lester reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21211617; Phenotypes: Short rib polydactyly syndrome (SRPS) type 3 with or without polydactyly, 613091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DYM Tracy Lester reviewed gene: DYM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Dyggve-Melchior-Clausen disease 223800, Smith-McCort dysplasia 607326; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DVL3 Tracy Lester reviewed gene: DVL3: Rating: GREEN; Mode of pathogenicity: ; Publications: 26924530; Phenotypes: Robinow syndrome, autosomal dominant 3, 616894; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 DVL1 Tracy Lester reviewed gene: DVL1: Rating: GREEN; Mode of pathogenicity: ; Publications: 25817014, 25817016; Phenotypes: Robinow syndrome, autosomal dominant 2 616331; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v1.147 DPM1 Tracy Lester reviewed gene: DPM1: Rating: GREEN; Mode of pathogenicity: ; Publications: 10642602, 15669674, 23856421; Phenotypes: Congenital disorder of glycosylation, type Ie 608799; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DOCK6 Tracy Lester reviewed gene: DOCK6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Adams-Oliver syndrome 2 614219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DNMT3A Tracy Lester reviewed gene: DNMT3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Tatton-Brown-Rahman syndrome 615879; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 DMP1 Tracy Lester reviewed gene: DMP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypophosphatemic rickets, AR, 241520; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DLX6 Tracy Lester reviewed gene: DLX6: Rating: AMBER; Mode of pathogenicity: ; Publications: 28611547; Phenotypes: Split-hand/foot malformation 1 183600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 DLX5 Tracy Lester reviewed gene: DLX5: Rating: GREEN; Mode of pathogenicity: ; Publications: 27085093; Phenotypes: Split-hand/foot malformation 1 with sensorineural hearing loss 220600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DLX3 Tracy Lester reviewed gene: DLX3: Rating: GREEN; Mode of pathogenicity: ; Publications: 26762616, 26104267; Phenotypes: Amelogenesis imperfecta, type IV 104510, Trichodontoosseous syndrome 190320; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 DLL4 Tracy Lester reviewed gene: DLL4: Rating: GREEN; Mode of pathogenicity: ; Publications: 26299364; Phenotypes: Adams-Oliver syndrome 6, 616589; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 DLL3 Tracy Lester reviewed gene: DLL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylocostal dysostosis 1, autosomal recessive 277300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DIS3L2 Tracy Lester reviewed gene: DIS3L2: Rating: GREEN; Mode of pathogenicity: ; Publications: 22306653; Phenotypes: Perlman syndrome 267000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DHODH Tracy Lester reviewed gene: DHODH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Miller syndrome (postaxial acrofacial dysostosis) 263750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DHCR24 Tracy Lester reviewed gene: DHCR24: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Desmosterolosis 602398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DDR2 Tracy Lester reviewed gene: DDR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylometaepiphyseal dysplasia, short limb-hand type 271665, at least 3 cases reported; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 DCC Tracy Lester reviewed gene: DCC: Rating: AMBER; Mode of pathogenicity: ; Publications: 28250456; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 2 617542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CYP27B1 Tracy Lester reviewed gene: CYP27B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Vitamin D-dependent rickets, type I 264700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CUL7 Tracy Lester reviewed gene: CUL7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: 3-M syndrome 1 273750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CTSK Tracy Lester reviewed gene: CTSK: Rating: GREEN; Mode of pathogenicity: ; Publications: 28328823; Phenotypes: Pycnodysostosis 265800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CTSC Tracy Lester reviewed gene: CTSC: Rating: GREEN; Mode of pathogenicity: ; Publications: 15727652, 26205983, 24966751; Phenotypes: Haim-Munk syndrome 245010, ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CTSA Tracy Lester reviewed gene: CTSA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Galactosialidosis 256540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CSPP1 Tracy Lester reviewed gene: CSPP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 24360803, 24360808; Phenotypes: Joubert syndrome 21 615636, ORPHA:475 Joubert syndrome, ORPHA:397715 Joubert syndrome with Jeune asphyxiating thoracic dystrophy, ORPHA:564 Meckel syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CRTAP Tracy Lester reviewed gene: CRTAP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteogenesis imperfecta, type VII 610682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CREBBP Tracy Lester reviewed gene: CREBBP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Rubinstein-Taybi syndrome 180849; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 CREB3L1 Tracy Lester reviewed gene: CREB3L1: Rating: AMBER; Mode of pathogenicity: ; Publications: 25007323, 28817112, 29936144.; Phenotypes: Osteogenesis imperfecta, type XVI 616229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 COMP Tracy Lester reviewed gene: COMP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Epiphyseal dysplasia, multiple, 1 132400, Pseudoachondroplasia 177170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 COLEC11 Tracy Lester reviewed gene: COLEC11: Rating: GREEN; Mode of pathogenicity: ; Publications: 21258343, 28301481, 8933348, 2569826; Phenotypes: 3MC syndrome 2 265050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 COLEC10 Tracy Lester reviewed gene: COLEC10: Rating: AMBER; Mode of pathogenicity: ; Publications: 28301481; Phenotypes: 3MC syndrome 3 -248340; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 COL9A3 Tracy Lester reviewed gene: COL9A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: MED, multiple epiphyseal dysplasia 3, with or without myopathy - 600969; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 COL9A2 Tracy Lester reviewed gene: COL9A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Stickler syndrome, type V 614284, Epiphyseal dysplasia, multiple, 2 600204, {Intervertebral disc disease, susceptibility to}, 603932, Stickler syndrome, type V, 614284; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 COL9A1 Tracy Lester reviewed gene: COL9A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Epiphyseal dysplasia, multiple, 6 614135, Stickler syndrome, type IV 614134; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 COL2A1 Tracy Lester reviewed gene: COL2A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Achondrogenesis, type II or hypochondrogenesis 200610, Avascular necrosis of the femoral head 608805, Czech dysplasia 609162, Epiphyseal dysplasia, multiple, with myopia and deafness 132450, Kniest dysplasia 156550, Legg-Calve-Perthes disease 150600, Osteoarthritis with mild chondrodysplasia 604864, Otospondylomegaepiphyseal dysplasia 215150, Platyspondylic skeletal dysplasia, Torrance type 151210, SED congenita 183900, SMED Strudwick type 184250, Spondyloepiphyseal dysplasia, Stanescu type 616583, Spondyloperipheral dysplasia 271700, Stickler sydrome, type I, nonsyndromic ocular 609508, Stickler syndrome, type I 108300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 COL1A2 Tracy Lester reviewed gene: COL1A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Ehlers-Danlos syndrome, cardiac valvular form 225320, Ehlers-Danlos syndrome, type VIIB 130060, Osteogenesis imperfecta, type II 166210, Osteogenesis imperfecta, type III 259420, Osteogenesis imperfecta, type IV 166220; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal OR MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted (if exclude 255320)
Skeletal dysplasia v1.147 COL1A1 Tracy Lester reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Caffey disease 114000, Ehlers-Danlos syndrome, classic 130000, Ehlers-Danlos syndrome, type VIIA 130060, Osteogenesis imperfecta, type I 166200, Osteogenesis imperfecta, type II 166210, Osteogenesis imperfecta, type III 259420, Osteogenesis imperfecta, type IV 166220; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v1.147 COL11A2 Tracy Lester reviewed gene: COL11A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Fibrochondrogenesis 2 614524?, Otospondylomegaepiphyseal dysplasia 215150, Stickler syndrome, type III 184840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 COL11A1 Tracy Lester reviewed gene: COL11A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Fibrochondrogenesis 1 228520, Marshall syndrome 154780, Stickler syndrome, type II 604841; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 COL10A1 Tracy Lester reviewed gene: COL10A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Metaphyseal chondrodysplasia, Schmid type 156500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 COG1 Tracy Lester reviewed gene: COG1: Rating: GREEN; Mode of pathogenicity: ; Publications: 16537452, 19008299; Phenotypes: Congenital disorder of glycosylation, type IIg 611209; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CLCN7 Tracy Lester reviewed gene: CLCN7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteopetrosis, autosomal dominant 2 166600, Osteopetrosis, autosomal recessive 4 611490; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CLCN5 Tracy Lester reviewed gene: CLCN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Dent disease 300009, Hypophosphatemic rickets 300554, Nephrolithiasis, type I 310468, Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis 308990; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v1.147 CKAP2L Tracy Lester reviewed gene: CKAP2L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Syndactyly with microcephaly and MR (Filippi syndrome) 272440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CHSY1 Tracy Lester reviewed gene: CHSY1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Temtamy preaxial brachydactyly syndrome 605282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CHST3 Tracy Lester reviewed gene: CHST3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondyloepiphyseal dysplasia with congenital joint dislocations (recessive Larsen syndrome) 143095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CHST14 Tracy Lester reviewed gene: CHST14: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Ehlers-Danlos syndrome, musculocontractural type 1 601776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 C21orf2 Tracy Lester reviewed gene: C21orf2: Rating: GREEN; Mode of pathogenicity: ; Publications: 26974433; Phenotypes: Spondylometaphyseal dysplasia, axial 602271; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CEP290 Tracy Lester reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome 14 615991, Joubert syndrome 5 610188, Leber congenital amaurosis 10, Meckel syndrome 4 611134, Senior-Loken syndrome 6 610189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CEP120 Tracy Lester reviewed gene: CEP120: Rating: AMBER; Mode of pathogenicity: ; Publications: 27208211, 27208211; Phenotypes: Short-rib thoracic dysplasia 13 with or without polydactyly 616300, Joubert syndrome 213300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CDT1 Tracy Lester reviewed gene: CDT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Meier-Gorlin syndrome 4 613804; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CDKN1C Tracy Lester reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: IMAGE syndrome 614732; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted?? No - Paternally imprinted
Skeletal dysplasia v1.147 CDH3 Tracy Lester reviewed gene: CDH3: Rating: GREEN; Mode of pathogenicity: ; Publications: 15805154, 22140374; Phenotypes: Ectodermal dysplasia, ectrodactyly, and macular dystrophy 225280; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CD96 Tracy Lester reviewed gene: CD96: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: C-syndrome 217750 (opitz trigonocephaly); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 CDC45 Tracy Lester reviewed gene: CDC45: Rating: GREEN; Mode of pathogenicity: ; Publications: 27374770; Phenotypes: Meier-Gorlin syndrome with craniosynostosis (from PMID 27374770), Craniosynostosis (Wilkie) (from Ana Beleza); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CCDC8 Tracy Lester reviewed gene: CCDC8: Rating: GREEN; Mode of pathogenicity: ; Publications: 21737058; Phenotypes: 3-M syndrome 3, 614205; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CC2D2A Tracy Lester reviewed gene: CC2D2A: Rating: GREEN; Mode of pathogenicity: ; Publications: 18513680, 24706459, 23351400; Phenotypes: Meckel syndrome 6 612284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CASR Tracy Lester reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyperparathyroidism, neonatal 239200, Hypocalcemia, autosomal dominant 601198, Hypocalcemia, autosomal dominant, with Bartter syndrome 601198, Hypocalciuric hypercalcemia, type I 145980; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CANT1 Tracy Lester reviewed gene: CANT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Desbuquois dysplasia 1 251450, multiple epiphyseal dysplasia type 7, 617719.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 CA2 Tracy Lester reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis 259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 C2CD3 Tracy Lester reviewed gene: C2CD3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Orofaciodigital syndrome XIV 615948; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 BMPR1B Tracy Lester reviewed gene: BMPR1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Acromesomelic dysplasia, Demirhan type 609441, Brachydactyly, type A1, D 616849, Brachydactyly, type A2 112600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 BMPER Tracy Lester reviewed gene: BMPER: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Diaphanospondylodysostosis 608022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 BMP2 Tracy Lester reviewed gene: BMP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 19327734, 21357617, 29198724; Phenotypes: Brachydactyly, type A2 112600, {HFE hemochromatosis, modifier of} 235200, short stature, facial dysmorphism and skeletal anomalies with or without cardiac aomalies 617877.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 BMP1 Tracy Lester reviewed gene: BMP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteogenesis imperfecta, type XIII, 614856; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 BHLHA9 Tracy Lester reviewed gene: BHLHA9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Syndactyly, mesoaxial synostotic, with phalangeal reduction 609432; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 B9D1 Tracy Lester reviewed gene: B9D1: Rating: RED; Mode of pathogenicity: ; Publications: 24886560, 21493627; Phenotypes: Meckel syndrome 9 614209; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 B4GALT7 Tracy Lester reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Ehlers-Danlos syndrome with short stature and limb anomalies 130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 B3GAT3 Tracy Lester reviewed gene: B3GAT3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Larsen alike phenotype (skd incl), Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects, 245600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 B3GALT6 Tracy Lester reviewed gene: B3GALT6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Ehlers-Danlos syndrome, progeroid type, 2 615349, Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures 271640; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ATP7A Tracy Lester reviewed gene: ATP7A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Menkes disease 309400, Occipital horn syndrome 304150, Spinal muscular atrophy, distal, 300489; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v1.147 ATP6V0A2 Tracy Lester reviewed gene: ATP6V0A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cutis laxa, autosomal recessive, type IIA 219200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ASXL2 Tracy Lester reviewed gene: ASXL2: Rating: GREEN; Mode of pathogenicity: ; Publications: 27693232; Phenotypes: Shashi-Pena syndrome 617190; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v1.147 ASXL1 Tracy Lester reviewed gene: ASXL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bohring-Opitz syndrome 605039; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 ARSE Tracy Lester reviewed gene: ARSE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: CDPXL, Chondrodysplasia punctata, X-linked recessive, 302950, X-linked recessive chondrodysplasia punctata, CHONDRODYSPLASIA PUNCTATA 1, X-LINKED; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v1.147 ARSB Tracy Lester reviewed gene: ARSB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucopolysaccharidosis type VI (Maroteaux-Lamy) 253200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ARID1B Tracy Lester reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Coffin-Siris syndrome type 1 - 135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 ARHGAP31 Tracy Lester reviewed gene: ARHGAP31: Rating: GREEN; Mode of pathogenicity: ; Publications: 21565291, 29924900; Phenotypes: Adams-Oliver syndrome 1 100300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 ANTXR2 Tracy Lester reviewed gene: ANTXR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyaline fibromatosis syndrome 228600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ANO5 Tracy Lester reviewed gene: ANO5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Gnatodiaphyseal dysplasia, Osteogenesis Imperfecta and Decreased Bone Density, skeletal dysplasias, Disproportionate Short Stature; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ANKRD11 Tracy Lester reviewed gene: ANKRD11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: KBG syndrome 148050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 ANKH Tracy Lester reviewed gene: ANKH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Chondrocalcinosis 2 118600, Craniometaphyseal dysplasia 123000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 AMER1 Tracy Lester reviewed gene: AMER1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteopathia striata with cranial sclerosis 300373; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.147 ALX4 Tracy Lester reviewed gene: ALX4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Frontonasal dysplasia 2 613451; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 ALX3 Tracy Lester reviewed gene: ALX3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Frontonasal dysplasia 1 136760 (frontorhiny); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 ALX1 Tracy Lester reviewed gene: ALX1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Frontonasal dysplasia type 3 613456; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.147 ALPL Tracy Lester reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: hypophosphatasia, Osteogenesis Imperfecta and Decreased Bone Density, skeletal dysplasias; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ALG9 Tracy Lester reviewed gene: ALG9: Rating: GREEN; Mode of pathogenicity: ; Publications: 25966638; Phenotypes: Congenital disorder of glycosylation, type Il 608776, Gillessen-Kaesbach-Nishimura syndrome 263210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ALG3 Tracy Lester reviewed gene: ALG3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Id 601110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ALG12 Tracy Lester reviewed gene: ALG12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ig 607143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 AKT1 Tracy Lester reviewed gene: AKT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cowden syndrome 6 615109, Proteus syndrome, somatic 176920; Mode of inheritance: Unknown
Skeletal dysplasia v1.147 AGPS Tracy Lester reviewed gene: AGPS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Rhizomelic chondrodysplasia punctata, type 3 600121; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 AGA Tracy Lester reviewed gene: AGA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Aspartylglucosaminuria 208400 (Patients may be tall for their age, but lack of a growth spurt in puberty typically causes adults to be short); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ADAMTSL2 Tracy Lester reviewed gene: ADAMTSL2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Geleophysic dysplasia 1 231050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ADAMTS17 Tracy Lester reviewed gene: ADAMTS17: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Weill-Marchesani syndrome type 4; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ADAMTS10 Tracy Lester reviewed gene: ADAMTS10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Weill-Marchesani syndrome type 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ACVR1 Tracy Lester reviewed gene: ACVR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Fibrodysplasia ossificans progressiva 135100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.147 ACP5 Tracy Lester reviewed gene: ACP5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondyloenchondrodysplasia with immune dysregulation 607944; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ACAN Tracy Lester reviewed gene: ACAN: Rating: GREEN; Mode of pathogenicity: ; Publications: 24762113; Phenotypes: Osteochondritis dissecans, short stature, and early-onset osteoarthritis 165800, Spondyloepimetaphyseal dysplasia, aggrecan type 61283, Spondyloepiphyseal dysplasia, Kimberley type 608361; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 ABL1 Tracy Lester reviewed gene: ABL1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28288113; Phenotypes: Congenital heart defects and skeletal malformations syndrome, 617602; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v1.147 ABCC9 Tracy Lester reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypertrichotic osteochondrodysplasia 23985 (Cantu syndrome); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v1.146 ZMPSTE24 Eleanor Williams reviewed gene: ZMPSTE24: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ZIC1 Eleanor Williams reviewed gene: ZIC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 YY1 Eleanor Williams reviewed gene: YY1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 XYLT2 Eleanor Williams reviewed gene: XYLT2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 XYLT1 Eleanor Williams reviewed gene: XYLT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 XRCC4 Eleanor Williams reviewed gene: XRCC4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WNT7A Eleanor Williams reviewed gene: WNT7A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WNT5A Eleanor Williams reviewed gene: WNT5A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WNT3 Eleanor Williams reviewed gene: WNT3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WNT10B Eleanor Williams reviewed gene: WNT10B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WNT1 Eleanor Williams reviewed gene: WNT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WISP3 Eleanor Williams reviewed gene: WISP3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WDR60 Eleanor Williams reviewed gene: WDR60: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WDR35 Eleanor Williams reviewed gene: WDR35: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WDR34 Eleanor Williams reviewed gene: WDR34: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WDR19 Eleanor Williams reviewed gene: WDR19: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 UFSP2 Eleanor Williams reviewed gene: UFSP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TYROBP Eleanor Williams reviewed gene: TYROBP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TWIST2 Eleanor Williams reviewed gene: TWIST2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TWIST1 Eleanor Williams reviewed gene: TWIST1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TTC21B Eleanor Williams reviewed gene: TTC21B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TRPV4 Eleanor Williams reviewed gene: TRPV4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TRPS1 Eleanor Williams reviewed gene: TRPS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TRIP11 Eleanor Williams reviewed gene: TRIP11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TREM2 Eleanor Williams reviewed gene: TREM2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TRAPPC2 Eleanor Williams reviewed gene: TRAPPC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TP63 Eleanor Williams reviewed gene: TP63: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TNFSF11 Eleanor Williams reviewed gene: TNFSF11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TNFRSF11B Eleanor Williams reviewed gene: TNFRSF11B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TNFRSF11A Eleanor Williams reviewed gene: TNFRSF11A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TMEM67 Eleanor Williams reviewed gene: TMEM67: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TMEM38B Eleanor Williams reviewed gene: TMEM38B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TMEM231 Eleanor Williams reviewed gene: TMEM231: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TMEM216 Eleanor Williams reviewed gene: TMEM216: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TMEM165 Eleanor Williams reviewed gene: TMEM165: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TMCO1 Eleanor Williams reviewed gene: TMCO1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 THPO Eleanor Williams reviewed gene: THPO: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TGFBR2 Eleanor Williams reviewed gene: TGFBR2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TGFBR1 Eleanor Williams reviewed gene: TGFBR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TGFB2 Eleanor Williams reviewed gene: TGFB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TGFB1 Eleanor Williams reviewed gene: TGFB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TGDS Eleanor Williams reviewed gene: TGDS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TERT Eleanor Williams reviewed gene: TERT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TCTN3 Eleanor Williams reviewed gene: TCTN3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TCTN2 Eleanor Williams reviewed gene: TCTN2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TCTEX1D2 Eleanor Williams reviewed gene: TCTEX1D2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TCOF1 Eleanor Williams reviewed gene: TCOF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TCIRG1 Eleanor Williams reviewed gene: TCIRG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TCF12 Eleanor Williams reviewed gene: TCF12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TBXAS1 Eleanor Williams reviewed gene: TBXAS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TBX6 Eleanor Williams reviewed gene: TBX6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TBX5 Eleanor Williams reviewed gene: TBX5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TBX4 Eleanor Williams reviewed gene: TBX4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TBX3 Eleanor Williams reviewed gene: TBX3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TBX15 Eleanor Williams reviewed gene: TBX15: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TBCE Eleanor Williams reviewed gene: TBCE: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 TALDO1 Eleanor Williams reviewed gene: TALDO1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SUMF1 Eleanor Williams reviewed gene: SUMF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SULF1 Eleanor Williams reviewed gene: SULF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SP7 Eleanor Williams reviewed gene: SP7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SOX9 Eleanor Williams reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SOST Eleanor Williams reviewed gene: SOST: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SNX10 Eleanor Williams reviewed gene: SNX10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SNRPB Eleanor Williams reviewed gene: SNRPB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SMOC1 Eleanor Williams edited their review of gene: SMOC1: Added comment: This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: SMOC1; Initial rating suggestion: green; Changed rating: AMBER
Skeletal dysplasia v1.146 SMC3 Eleanor Williams reviewed gene: SMC3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SMC1A Eleanor Williams reviewed gene: SMC1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SMARCAL1 Eleanor Williams reviewed gene: SMARCAL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SMAD4 Eleanor Williams reviewed gene: SMAD4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SMAD3 Eleanor Williams reviewed gene: SMAD3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SLCO5A1 Eleanor Williams reviewed gene: SLCO5A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SLCO2A1 Eleanor Williams reviewed gene: SLCO2A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SLC39A13 Eleanor Williams reviewed gene: SLC39A13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SLC35D1 Eleanor Williams reviewed gene: SLC35D1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SLC34A3 Eleanor Williams reviewed gene: SLC34A3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SLC29A3 Eleanor Williams reviewed gene: SLC29A3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SLC26A2 Eleanor Williams reviewed gene: SLC26A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SLC17A5 Eleanor Williams reviewed gene: SLC17A5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SKI Eleanor Williams reviewed gene: SKI: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SHOX Eleanor Williams reviewed gene: SHOX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SH3PXD2B Eleanor Williams reviewed gene: SH3PXD2B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SH3BP2 Eleanor Williams reviewed gene: SH3BP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SGSH Eleanor Williams reviewed gene: SGSH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SFRP4 Eleanor Williams reviewed gene: SFRP4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SF3B4 Eleanor Williams reviewed gene: SF3B4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SETD2 Eleanor Williams reviewed gene: SETD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SERPINH1 Eleanor Williams reviewed gene: SERPINH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SERPINF1 Eleanor Williams reviewed gene: SERPINF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SEC24D Eleanor Williams reviewed gene: SEC24D: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SCARF2 Eleanor Williams reviewed gene: SCARF2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SBDS Eleanor Williams reviewed gene: SBDS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SALL4 Eleanor Williams reviewed gene: SALL4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 SALL1 Eleanor Williams reviewed gene: SALL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RUNX2 Eleanor Williams reviewed gene: RUNX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RPGRIP1L Eleanor Williams reviewed gene: RPGRIP1L: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ROR2 Eleanor Williams reviewed gene: ROR2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RNU4ATAC Eleanor Williams reviewed gene: RNU4ATAC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RMRP Eleanor Williams reviewed gene: RMRP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RIPPLY2 Eleanor Williams reviewed gene: RIPPLY2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RFT1 Eleanor Williams reviewed gene: RFT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RECQL4 Eleanor Williams reviewed gene: RECQL4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 WRN Eleanor Williams reviewed gene: WRN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RBPJ Eleanor Williams reviewed gene: RBPJ: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RBM8A Eleanor Williams reviewed gene: RBM8A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RASGRP2 Eleanor Williams reviewed gene: RASGRP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RAD21 Eleanor Williams reviewed gene: RAD21: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RAB33B Eleanor Williams reviewed gene: RAB33B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 RAB23 Eleanor Williams reviewed gene: RAB23: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PYCR1 Eleanor Williams reviewed gene: PYCR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PUF60 Eleanor Williams reviewed gene: PUF60: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PTPN11 Eleanor Williams reviewed gene: PTPN11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PTHLH Eleanor Williams reviewed gene: PTHLH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PTH1R Eleanor Williams reviewed gene: PTH1R: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PTDSS1 Eleanor Williams reviewed gene: PTDSS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PSPH Eleanor Williams reviewed gene: PSPH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PSAT1 Eleanor Williams reviewed gene: PSAT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PRMT7 Eleanor Williams reviewed gene: PRMT7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PRKAR1A Eleanor Williams reviewed gene: PRKAR1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PPIB Eleanor Williams reviewed gene: PPIB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 POR Eleanor Williams reviewed gene: POR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 POP1 Eleanor Williams reviewed gene: POP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 POLR1D Eleanor Williams reviewed gene: POLR1D: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 POLR1C Eleanor Williams reviewed gene: POLR1C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 POLR1A Eleanor Williams reviewed gene: POLR1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 POC1A Eleanor Williams reviewed gene: POC1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PLS3 Eleanor Williams reviewed gene: PLS3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PLOD2 Eleanor Williams reviewed gene: PLOD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PLEKHM1 Eleanor Williams reviewed gene: PLEKHM1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PITX1 Eleanor Williams reviewed gene: PITX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PIK3R1 Eleanor Williams reviewed gene: PIK3R1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PIK3CA Eleanor Williams reviewed gene: PIK3CA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PIGV Eleanor Williams reviewed gene: PIGV: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PIGT Eleanor Williams reviewed gene: PIGT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PHGDH Eleanor Williams reviewed gene: PHGDH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PHEX Eleanor Williams reviewed gene: PHEX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PGM3 Eleanor Williams reviewed gene: PGM3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PEX7 Eleanor Williams reviewed gene: PEX7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PEX5 Eleanor Williams reviewed gene: PEX5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PDE4D Eleanor Williams reviewed gene: PDE4D: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PDE3A Eleanor Williams reviewed gene: PDE3A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PCYT1A Eleanor Williams reviewed gene: PCYT1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PCNT Eleanor Williams reviewed gene: PCNT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PAPSS2 Eleanor Williams reviewed gene: PAPSS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 PAM16 Eleanor Williams reviewed gene: PAM16: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 P4HB Eleanor Williams reviewed gene: P4HB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 P3H1 Eleanor Williams reviewed gene: P3H1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 OSTM1 Eleanor Williams reviewed gene: OSTM1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ORC6 Eleanor Williams reviewed gene: ORC6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ORC4 Eleanor Williams reviewed gene: ORC4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ORC1 Eleanor Williams reviewed gene: ORC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 OFD1 Eleanor Williams reviewed gene: OFD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 OBSL1 Eleanor Williams reviewed gene: OBSL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 OAT Eleanor Williams reviewed gene: OAT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NSDHL Eleanor Williams reviewed gene: NSDHL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NSD1 Eleanor Williams reviewed gene: NSD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NPR2 Eleanor Williams reviewed gene: NPR2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NOTCH2 Eleanor Williams reviewed gene: NOTCH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NOTCH1 Eleanor Williams edited their review of gene: NOTCH1: Added comment: This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: NOTCH1; Initial rating suggestion: green; Changed rating: AMBER
Skeletal dysplasia v1.146 NOG Eleanor Williams reviewed gene: NOG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NLRP3 Eleanor Williams reviewed gene: NLRP3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NKX3-2 Eleanor Williams reviewed gene: NKX3-2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NIPBL Eleanor Williams reviewed gene: NIPBL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NIN Eleanor Williams reviewed gene: NIN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NFIX Eleanor Williams reviewed gene: NFIX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NF1 Eleanor Williams reviewed gene: NF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NEU1 Eleanor Williams reviewed gene: NEU1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NEK1 Eleanor Williams reviewed gene: NEK1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NANS Eleanor Williams reviewed gene: NANS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 NAGLU Eleanor Williams reviewed gene: NAGLU: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MYCN Eleanor Williams reviewed gene: MYCN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MSX2 Eleanor Williams reviewed gene: MSX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MPDU1 Eleanor Williams reviewed gene: MPDU1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MNX1 Eleanor Williams reviewed gene: MNX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MMP9 Eleanor Williams reviewed gene: MMP9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MMP2 Eleanor Williams reviewed gene: MMP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MMP13 Eleanor Williams reviewed gene: MMP13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MKS1 Eleanor Williams reviewed gene: MKS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MIR17HG Eleanor Williams reviewed gene: MIR17HG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MGP Eleanor Williams reviewed gene: MGP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MESP2 Eleanor Williams reviewed gene: MESP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MEOX1 Eleanor Williams reviewed gene: MEOX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MEGF8 Eleanor Williams reviewed gene: MEGF8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MATN3 Eleanor Williams reviewed gene: MATN3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MASP1 Eleanor Williams reviewed gene: MASP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MAP3K7 Eleanor Williams reviewed gene: MAP3K7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MAN2B1 Eleanor Williams reviewed gene: MAN2B1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 MAFB Eleanor Williams reviewed gene: MAFB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LTBP3 Eleanor Williams reviewed gene: LTBP3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LTBP2 Eleanor Williams reviewed gene: LTBP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LRP5 Eleanor Williams reviewed gene: LRP5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LRP4 Eleanor Williams reviewed gene: LRP4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LPIN2 Eleanor Williams reviewed gene: LPIN2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LONP1 Eleanor Williams reviewed gene: LONP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LMX1B Eleanor Williams reviewed gene: LMX1B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LMNA Eleanor Williams reviewed gene: LMNA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LMBR1 Eleanor Williams reviewed gene: LMBR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LIFR Eleanor Williams reviewed gene: LIFR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LFNG Eleanor Williams reviewed gene: LFNG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LEMD3 Eleanor Williams reviewed gene: LEMD3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 LBR Eleanor Williams reviewed gene: LBR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 KMT2D Eleanor Williams reviewed gene: KMT2D: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 KIF7 Eleanor Williams reviewed gene: KIF7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 KIF22 Eleanor Williams reviewed gene: KIF22: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 KAT6B Eleanor Williams reviewed gene: KAT6B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 KAT6A Eleanor Williams reviewed gene: KAT6A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 INPPL1 Eleanor Williams reviewed gene: INPPL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IMPAD1 Eleanor Williams reviewed gene: IMPAD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IL1RN Eleanor Williams reviewed gene: IL1RN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IL11RA Eleanor Williams reviewed gene: IL11RA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IKBKG Eleanor Williams reviewed gene: IKBKG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IHH Eleanor Williams reviewed gene: IHH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IGF1R Eleanor Williams reviewed gene: IGF1R: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IFT81 Eleanor Williams reviewed gene: IFT81: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IFT80 Eleanor Williams reviewed gene: IFT80: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IFT52 Eleanor Williams reviewed gene: IFT52: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IFT43 Eleanor Williams reviewed gene: IFT43: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IFT172 Eleanor Williams reviewed gene: IFT172: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IFT140 Eleanor Williams reviewed gene: IFT140: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IFT122 Eleanor Williams reviewed gene: IFT122: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IFITM5 Eleanor Williams reviewed gene: IFITM5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IFIH1 Eleanor Williams reviewed gene: IFIH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IDUA Eleanor Williams reviewed gene: IDUA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IDS Eleanor Williams reviewed gene: IDS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IDH2 Eleanor Williams reviewed gene: IDH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 IDH1 Eleanor Williams reviewed gene: IDH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ICK Eleanor Williams reviewed gene: ICK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HSPG2 Eleanor Williams reviewed gene: HSPG2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HNRNPK Eleanor Williams reviewed gene: HNRNPK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HPGD Eleanor Williams reviewed gene: HPGD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HOXD13 Eleanor Williams reviewed gene: HOXD13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HOXD11 Eleanor Williams reviewed gene: HOXD11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HOXA13 Eleanor Williams reviewed gene: HOXA13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HOXA11 Eleanor Williams reviewed gene: HOXA11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HGSNAT Eleanor Williams reviewed gene: HGSNAT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HES7 Eleanor Williams reviewed gene: HES7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HDAC8 Eleanor Williams reviewed gene: HDAC8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 HDAC4 Eleanor Williams reviewed gene: HDAC4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GZF1 Eleanor Williams reviewed gene: GZF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GUSB Eleanor Williams reviewed gene: GUSB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GSC Eleanor Williams reviewed gene: GSC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GPX4 Eleanor Williams reviewed gene: GPX4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GPC6 Eleanor Williams reviewed gene: GPC6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GORAB Eleanor Williams reviewed gene: GORAB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GNS Eleanor Williams reviewed gene: GNS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GNPTG Eleanor Williams reviewed gene: GNPTG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GNPTAB Eleanor Williams reviewed gene: GNPTAB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GNPAT Eleanor Williams reviewed gene: GNPAT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GNAS Eleanor Williams reviewed gene: GNAS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GLI3 Eleanor Williams reviewed gene: GLI3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GLB1 Eleanor Williams reviewed gene: GLB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GJA1 Eleanor Williams reviewed gene: GJA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GHR Eleanor Williams reviewed gene: GHR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GDF6 Eleanor Williams reviewed gene: GDF6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GDF5 Eleanor Williams reviewed gene: GDF5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GDF3 Eleanor Williams reviewed gene: GDF3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GALNT3 Eleanor Williams reviewed gene: GALNT3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 GALNS Eleanor Williams reviewed gene: GALNS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FZD2 Eleanor Williams reviewed gene: FZD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FUCA1 Eleanor Williams reviewed gene: FUCA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FN1 Eleanor Williams reviewed gene: FN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FLNB Eleanor Williams reviewed gene: FLNB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FLNA Eleanor Williams reviewed gene: FLNA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FKBP10 Eleanor Williams reviewed gene: FKBP10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FIG4 Eleanor Williams reviewed gene: FIG4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FGFR3 Eleanor Williams reviewed gene: FGFR3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FGFR2 Eleanor Williams reviewed gene: FGFR2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FGFR1 Eleanor Williams reviewed gene: FGFR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FGF23 Eleanor Williams reviewed gene: FGF23: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FGF16 Eleanor Williams reviewed gene: FGF16: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FGF10 Eleanor Williams reviewed gene: FGF10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FGF9 Eleanor Williams reviewed gene: FGF9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FERMT3 Eleanor Williams reviewed gene: FERMT3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FBN2 Eleanor Williams reviewed gene: FBN2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FBN1 Eleanor Williams reviewed gene: FBN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FBLN1 Eleanor Williams reviewed gene: FBLN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FBLIM1 Eleanor Williams reviewed gene: FBLIM1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FAM58A Eleanor Williams reviewed gene: FAM58A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FAM20C Eleanor Williams reviewed gene: FAM20C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 FAM111A Eleanor Williams reviewed gene: FAM111A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EZH2 Eleanor Williams reviewed gene: EZH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EXTL3 Eleanor Williams reviewed gene: EXTL3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EXT2 Eleanor Williams reviewed gene: EXT2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EXT1 Eleanor Williams reviewed gene: EXT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EVC2 Eleanor Williams reviewed gene: EVC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EVC Eleanor Williams reviewed gene: EVC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ESCO2 Eleanor Williams reviewed gene: ESCO2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ERF Eleanor Williams reviewed gene: ERF: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EP300 Eleanor Williams reviewed gene: EP300: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EOGT Eleanor Williams reviewed gene: EOGT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ENPP1 Eleanor Williams reviewed gene: ENPP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EIF2AK3 Eleanor Williams reviewed gene: EIF2AK3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EFTUD2 Eleanor Williams reviewed gene: EFTUD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EFNB1 Eleanor Williams reviewed gene: EFNB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EED Eleanor Williams reviewed gene: EED: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 EBP Eleanor Williams reviewed gene: EBP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DYNC2LI1 Eleanor Williams reviewed gene: DYNC2LI1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DYNC2H1 Eleanor Williams reviewed gene: DYNC2H1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DYM Eleanor Williams reviewed gene: DYM: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DVL3 Eleanor Williams reviewed gene: DVL3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DVL1 Eleanor Williams reviewed gene: DVL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DPM1 Eleanor Williams reviewed gene: DPM1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DOCK6 Eleanor Williams reviewed gene: DOCK6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DNMT3A Eleanor Williams reviewed gene: DNMT3A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DMP1 Eleanor Williams reviewed gene: DMP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DLX6 Eleanor Williams reviewed gene: DLX6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DLX5 Eleanor Williams reviewed gene: DLX5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DLX3 Eleanor Williams reviewed gene: DLX3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DLL4 Eleanor Williams reviewed gene: DLL4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DLL3 Eleanor Williams reviewed gene: DLL3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DIS3L2 Eleanor Williams reviewed gene: DIS3L2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DHODH Eleanor Williams reviewed gene: DHODH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DHCR24 Eleanor Williams reviewed gene: DHCR24: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DDR2 Eleanor Williams reviewed gene: DDR2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 DCC Eleanor Williams reviewed gene: DCC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CYP27B1 Eleanor Williams reviewed gene: CYP27B1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CUL7 Eleanor Williams reviewed gene: CUL7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CTSK Eleanor Williams reviewed gene: CTSK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CTSC Eleanor Williams reviewed gene: CTSC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CTSA Eleanor Williams reviewed gene: CTSA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CSPP1 Eleanor Williams reviewed gene: CSPP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CRTAP Eleanor Williams reviewed gene: CRTAP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CREBBP Eleanor Williams reviewed gene: CREBBP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CREB3L1 Eleanor Williams reviewed gene: CREB3L1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COMP Eleanor Williams reviewed gene: COMP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COLEC11 Eleanor Williams reviewed gene: COLEC11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COLEC10 Eleanor Williams reviewed gene: COLEC10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COL9A3 Eleanor Williams reviewed gene: COL9A3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COL9A2 Eleanor Williams reviewed gene: COL9A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COL9A1 Eleanor Williams reviewed gene: COL9A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COL2A1 Eleanor Williams reviewed gene: COL2A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COL1A2 Eleanor Williams reviewed gene: COL1A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COL1A1 Eleanor Williams reviewed gene: COL1A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COL11A2 Eleanor Williams reviewed gene: COL11A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COL11A1 Eleanor Williams reviewed gene: COL11A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COL10A1 Eleanor Williams reviewed gene: COL10A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 COG1 Eleanor Williams reviewed gene: COG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CLCN7 Eleanor Williams reviewed gene: CLCN7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CLCN5 Eleanor Williams reviewed gene: CLCN5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CKAP2L Eleanor Williams reviewed gene: CKAP2L: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CHSY1 Eleanor Williams reviewed gene: CHSY1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CHST3 Eleanor Williams reviewed gene: CHST3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CHST14 Eleanor Williams reviewed gene: CHST14: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 C21orf2 Eleanor Williams reviewed gene: C21orf2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CEP290 Eleanor Williams reviewed gene: CEP290: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CEP120 Eleanor Williams reviewed gene: CEP120: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CDT1 Eleanor Williams reviewed gene: CDT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CDKN1C Eleanor Williams reviewed gene: CDKN1C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CDH3 Eleanor Williams reviewed gene: CDH3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CD96 Eleanor Williams reviewed gene: CD96: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CDC45 Eleanor Williams reviewed gene: CDC45: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CCDC8 Eleanor Williams reviewed gene: CCDC8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CC2D2A Eleanor Williams reviewed gene: CC2D2A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CASR Eleanor Williams reviewed gene: CASR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CANT1 Eleanor Williams reviewed gene: CANT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 CA2 Eleanor Williams reviewed gene: CA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 C2CD3 Eleanor Williams reviewed gene: C2CD3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 BMPR1B Eleanor Williams reviewed gene: BMPR1B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 BMPER Eleanor Williams reviewed gene: BMPER: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 BMP2 Eleanor Williams edited their review of gene: BMP2: Added comment: This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: BMP2; Initial rating suggestion: green; Changed rating: AMBER
Skeletal dysplasia v1.146 BMP1 Eleanor Williams reviewed gene: BMP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 BHLHA9 Eleanor Williams reviewed gene: BHLHA9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 B9D1 Eleanor Williams reviewed gene: B9D1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 B4GALT7 Eleanor Williams reviewed gene: B4GALT7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 B3GAT3 Eleanor Williams reviewed gene: B3GAT3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 B3GALT6 Eleanor Williams reviewed gene: B3GALT6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ATP7A Eleanor Williams reviewed gene: ATP7A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ATP6V0A2 Eleanor Williams reviewed gene: ATP6V0A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ASXL2 Eleanor Williams reviewed gene: ASXL2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ASXL1 Eleanor Williams reviewed gene: ASXL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ARSE Eleanor Williams reviewed gene: ARSE: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ARSB Eleanor Williams reviewed gene: ARSB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ARID1B Eleanor Williams reviewed gene: ARID1B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ARHGAP31 Eleanor Williams edited their review of gene: ARHGAP31: Added comment: This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: ARHGAP31; Initial rating suggestion: green; Changed rating: AMBER
Skeletal dysplasia v1.146 ANTXR2 Eleanor Williams reviewed gene: ANTXR2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ANO5 Eleanor Williams reviewed gene: ANO5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ANKRD11 Eleanor Williams reviewed gene: ANKRD11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ANKH Eleanor Williams reviewed gene: ANKH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 AMER1 Eleanor Williams reviewed gene: AMER1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ALX4 Eleanor Williams reviewed gene: ALX4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ALX3 Eleanor Williams reviewed gene: ALX3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ALX1 Eleanor Williams reviewed gene: ALX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ALPL Eleanor Williams reviewed gene: ALPL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ALG9 Eleanor Williams reviewed gene: ALG9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ALG3 Eleanor Williams reviewed gene: ALG3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ALG12 Eleanor Williams reviewed gene: ALG12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 AKT1 Eleanor Williams reviewed gene: AKT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 AGPS Eleanor Williams reviewed gene: AGPS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 AGA Eleanor Williams reviewed gene: AGA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ADAMTSL2 Eleanor Williams reviewed gene: ADAMTSL2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ADAMTS17 Eleanor Williams reviewed gene: ADAMTS17: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ADAMTS10 Eleanor Williams reviewed gene: ADAMTS10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ACVR1 Eleanor Williams reviewed gene: ACVR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ACP5 Eleanor Williams reviewed gene: ACP5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ACAN Eleanor Williams reviewed gene: ACAN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ABL1 Eleanor Williams reviewed gene: ABL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.146 ABCC9 Eleanor Williams reviewed gene: ABCC9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.145 ZMPSTE24 Eleanor Williams Source NHS GMS was added to ZMPSTE24.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ZIC1 Eleanor Williams Source NHS GMS was added to ZIC1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 YY1 Eleanor Williams Source NHS GMS was added to YY1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 XYLT2 Eleanor Williams Source NHS GMS was added to XYLT2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 XYLT1 Eleanor Williams Source NHS GMS was added to XYLT1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 XRCC4 Eleanor Williams Source NHS GMS was added to XRCC4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 WNT7A Eleanor Williams Source NHS GMS was added to WNT7A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 WNT5A Eleanor Williams Source NHS GMS was added to WNT5A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 WNT3 Eleanor Williams Source NHS GMS was added to WNT3.
Skeletal dysplasia v1.145 WNT10B Eleanor Williams Source NHS GMS was added to WNT10B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 WNT1 Eleanor Williams Source NHS GMS was added to WNT1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 WISP3 Eleanor Williams Source NHS GMS was added to WISP3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 WDR60 Eleanor Williams Source NHS GMS was added to WDR60.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 WDR35 Eleanor Williams Source NHS GMS was added to WDR35.
Skeletal dysplasia v1.145 WDR34 Eleanor Williams Source NHS GMS was added to WDR34.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 WDR19 Eleanor Williams Source NHS GMS was added to WDR19.
Skeletal dysplasia v1.145 UFSP2 Eleanor Williams gene: UFSP2 was added
gene: UFSP2 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: UFSP2 was set to
Skeletal dysplasia v1.145 TYROBP Eleanor Williams Source NHS GMS was added to TYROBP.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TWIST2 Eleanor Williams Source NHS GMS was added to TWIST2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TWIST1 Eleanor Williams Source NHS GMS was added to TWIST1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TTC21B Eleanor Williams Source NHS GMS was added to TTC21B.
Skeletal dysplasia v1.145 TRPV4 Eleanor Williams Source NHS GMS was added to TRPV4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TRPS1 Eleanor Williams Source NHS GMS was added to TRPS1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TRIP11 Eleanor Williams Source NHS GMS was added to TRIP11.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TREM2 Eleanor Williams Source NHS GMS was added to TREM2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TRAPPC2 Eleanor Williams Source NHS GMS was added to TRAPPC2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TP63 Eleanor Williams Source NHS GMS was added to TP63.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TNFSF11 Eleanor Williams Source NHS GMS was added to TNFSF11.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TNFRSF11B Eleanor Williams Source NHS GMS was added to TNFRSF11B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TNFRSF11A Eleanor Williams Source NHS GMS was added to TNFRSF11A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TMEM67 Eleanor Williams Source NHS GMS was added to TMEM67.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TMEM38B Eleanor Williams Source NHS GMS was added to TMEM38B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TMEM231 Eleanor Williams Source NHS GMS was added to TMEM231.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TMEM216 Eleanor Williams Source NHS GMS was added to TMEM216.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TMEM165 Eleanor Williams Source NHS GMS was added to TMEM165.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TMCO1 Eleanor Williams Source NHS GMS was added to TMCO1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 THPO Eleanor Williams Source NHS GMS was added to THPO.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TGFBR2 Eleanor Williams Source NHS GMS was added to TGFBR2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TGFBR1 Eleanor Williams Source NHS GMS was added to TGFBR1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TGFB2 Eleanor Williams Source NHS GMS was added to TGFB2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TGFB1 Eleanor Williams Source NHS GMS was added to TGFB1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TGDS Eleanor Williams gene: TGDS was added
gene: TGDS was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: TGDS was set to
Skeletal dysplasia v1.145 TERT Eleanor Williams Source NHS GMS was added to TERT.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TCTN3 Eleanor Williams Source NHS GMS was added to TCTN3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TCTN2 Eleanor Williams Source NHS GMS was added to TCTN2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TCTEX1D2 Eleanor Williams Source NHS GMS was added to TCTEX1D2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TCOF1 Eleanor Williams Source NHS GMS was added to TCOF1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TCIRG1 Eleanor Williams Source NHS GMS was added to TCIRG1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TCF12 Eleanor Williams Source NHS GMS was added to TCF12.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TBXAS1 Eleanor Williams Source NHS GMS was added to TBXAS1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TBX6 Eleanor Williams Source NHS GMS was added to TBX6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TBX5 Eleanor Williams Source NHS GMS was added to TBX5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TBX4 Eleanor Williams Source NHS GMS was added to TBX4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TBX3 Eleanor Williams Source NHS GMS was added to TBX3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TBX15 Eleanor Williams Source NHS GMS was added to TBX15.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TBCE Eleanor Williams Source NHS GMS was added to TBCE.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 TALDO1 Eleanor Williams Source NHS GMS was added to TALDO1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SUMF1 Eleanor Williams Source NHS GMS was added to SUMF1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SULF1 Eleanor Williams Source NHS GMS was added to SULF1.
Skeletal dysplasia v1.145 SP7 Eleanor Williams Source NHS GMS was added to SP7.
Skeletal dysplasia v1.145 SOX9 Eleanor Williams Source NHS GMS was added to SOX9.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SOST Eleanor Williams Source NHS GMS was added to SOST.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SNX10 Eleanor Williams Source NHS GMS was added to SNX10.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SNRPB Eleanor Williams Source NHS GMS was added to SNRPB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SMOC1 Eleanor Williams Source NHS GMS was added to SMOC1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SMC3 Eleanor Williams Source NHS GMS was added to SMC3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SMC1A Eleanor Williams Source NHS GMS was added to SMC1A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SMARCAL1 Eleanor Williams Source NHS GMS was added to SMARCAL1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SMAD4 Eleanor Williams Source NHS GMS was added to SMAD4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SMAD3 Eleanor Williams Source NHS GMS was added to SMAD3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SLCO5A1 Eleanor Williams Source NHS GMS was added to SLCO5A1.
Skeletal dysplasia v1.145 SLCO2A1 Eleanor Williams Source NHS GMS was added to SLCO2A1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SLC39A13 Eleanor Williams Source NHS GMS was added to SLC39A13.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SLC35D1 Eleanor Williams Source NHS GMS was added to SLC35D1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SLC34A3 Eleanor Williams Source NHS GMS was added to SLC34A3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SLC29A3 Eleanor Williams Source NHS GMS was added to SLC29A3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SLC26A2 Eleanor Williams Source NHS GMS was added to SLC26A2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SLC17A5 Eleanor Williams Source NHS GMS was added to SLC17A5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SKI Eleanor Williams Source NHS GMS was added to SKI.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SHOX Eleanor Williams Source NHS GMS was added to SHOX.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SH3PXD2B Eleanor Williams Source NHS GMS was added to SH3PXD2B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SH3BP2 Eleanor Williams Source NHS GMS was added to SH3BP2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SGSH Eleanor Williams Source NHS GMS was added to SGSH.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SFRP4 Eleanor Williams Source NHS GMS was added to SFRP4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SF3B4 Eleanor Williams Source NHS GMS was added to SF3B4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SETD2 Eleanor Williams Source NHS GMS was added to SETD2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SERPINH1 Eleanor Williams Source NHS GMS was added to SERPINH1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SERPINF1 Eleanor Williams Source NHS GMS was added to SERPINF1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SEC24D Eleanor Williams Source NHS GMS was added to SEC24D.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SCARF2 Eleanor Williams Source NHS GMS was added to SCARF2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SBDS Eleanor Williams Source NHS GMS was added to SBDS.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SALL4 Eleanor Williams Source NHS GMS was added to SALL4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 SALL1 Eleanor Williams Source NHS GMS was added to SALL1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 RUNX2 Eleanor Williams Source NHS GMS was added to RUNX2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 RPGRIP1L Eleanor Williams Source NHS GMS was added to RPGRIP1L.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ROR2 Eleanor Williams Source NHS GMS was added to ROR2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 RNU4ATAC Eleanor Williams Source NHS GMS was added to RNU4ATAC.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 RMRP Eleanor Williams Source NHS GMS was added to RMRP.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 RIPPLY2 Eleanor Williams gene: RIPPLY2 was added
gene: RIPPLY2 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: RIPPLY2 was set to
Skeletal dysplasia v1.145 RFT1 Eleanor Williams Source NHS GMS was added to RFT1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 RECQL4 Eleanor Williams Source NHS GMS was added to RECQL4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 WRN Eleanor Williams gene: WRN was added
gene: WRN was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: WRN was set to
Skeletal dysplasia v1.145 RBPJ Eleanor Williams Source NHS GMS was added to RBPJ.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 RBM8A Eleanor Williams Source NHS GMS was added to RBM8A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 RASGRP2 Eleanor Williams Source NHS GMS was added to RASGRP2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 RAD21 Eleanor Williams Source NHS GMS was added to RAD21.
Skeletal dysplasia v1.145 RAB33B Eleanor Williams Source NHS GMS was added to RAB33B.
Skeletal dysplasia v1.145 RAB23 Eleanor Williams Source NHS GMS was added to RAB23.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PYCR1 Eleanor Williams Source NHS GMS was added to PYCR1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PUF60 Eleanor Williams Source NHS GMS was added to PUF60.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PTPN11 Eleanor Williams Source NHS GMS was added to PTPN11.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PTHLH Eleanor Williams Source NHS GMS was added to PTHLH.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PTH1R Eleanor Williams Source NHS GMS was added to PTH1R.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PTDSS1 Eleanor Williams Source NHS GMS was added to PTDSS1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PSPH Eleanor Williams Source NHS GMS was added to PSPH.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PSAT1 Eleanor Williams Source NHS GMS was added to PSAT1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PRMT7 Eleanor Williams Source NHS GMS was added to PRMT7.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PRKAR1A Eleanor Williams Source NHS GMS was added to PRKAR1A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PPIB Eleanor Williams Source NHS GMS was added to PPIB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 POR Eleanor Williams Source NHS GMS was added to POR.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 POP1 Eleanor Williams Source NHS GMS was added to POP1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 POLR1D Eleanor Williams Source NHS GMS was added to POLR1D.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 POLR1C Eleanor Williams Source NHS GMS was added to POLR1C.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 POLR1A Eleanor Williams Source NHS GMS was added to POLR1A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 POC1A Eleanor Williams Source NHS GMS was added to POC1A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PLS3 Eleanor Williams Source NHS GMS was added to PLS3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PLOD2 Eleanor Williams Source NHS GMS was added to PLOD2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PLEKHM1 Eleanor Williams Source NHS GMS was added to PLEKHM1.
Skeletal dysplasia v1.145 PITX1 Eleanor Williams Source NHS GMS was added to PITX1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PIK3R1 Eleanor Williams Source NHS GMS was added to PIK3R1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PIK3CA Eleanor Williams gene: PIK3CA was added
gene: PIK3CA was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: PIK3CA was set to
Skeletal dysplasia v1.145 PIGV Eleanor Williams Source NHS GMS was added to PIGV.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PIGT Eleanor Williams Source NHS GMS was added to PIGT.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PHGDH Eleanor Williams Source NHS GMS was added to PHGDH.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PHEX Eleanor Williams Source NHS GMS was added to PHEX.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PGM3 Eleanor Williams Source NHS GMS was added to PGM3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PEX7 Eleanor Williams Source NHS GMS was added to PEX7.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PEX5 Eleanor Williams Source NHS GMS was added to PEX5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PDE4D Eleanor Williams Source NHS GMS was added to PDE4D.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PDE3A Eleanor Williams Source NHS GMS was added to PDE3A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PCYT1A Eleanor Williams Source NHS GMS was added to PCYT1A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PCNT Eleanor Williams Source NHS GMS was added to PCNT.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PAPSS2 Eleanor Williams Source NHS GMS was added to PAPSS2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 PAM16 Eleanor Williams Source NHS GMS was added to PAM16.
Skeletal dysplasia v1.145 P4HB Eleanor Williams Source NHS GMS was added to P4HB.
Skeletal dysplasia v1.145 P3H1 Eleanor Williams Source NHS GMS was added to P3H1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 OSTM1 Eleanor Williams Source NHS GMS was added to OSTM1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ORC6 Eleanor Williams Source NHS GMS was added to ORC6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ORC4 Eleanor Williams Source NHS GMS was added to ORC4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ORC1 Eleanor Williams Source NHS GMS was added to ORC1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 OFD1 Eleanor Williams Source NHS GMS was added to OFD1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 OBSL1 Eleanor Williams Source NHS GMS was added to OBSL1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 OAT Eleanor Williams gene: OAT was added
gene: OAT was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: OAT was set to
Skeletal dysplasia v1.145 NSDHL Eleanor Williams Source NHS GMS was added to NSDHL.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NSD1 Eleanor Williams Source NHS GMS was added to NSD1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NPR2 Eleanor Williams Source NHS GMS was added to NPR2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NOTCH2 Eleanor Williams Source NHS GMS was added to NOTCH2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NOTCH1 Eleanor Williams Source NHS GMS was added to NOTCH1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NOG Eleanor Williams Source NHS GMS was added to NOG.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NLRP3 Eleanor Williams Source NHS GMS was added to NLRP3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NKX3-2 Eleanor Williams Source NHS GMS was added to NKX3-2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NIPBL Eleanor Williams Source NHS GMS was added to NIPBL.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NIN Eleanor Williams Source NHS GMS was added to NIN.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NFIX Eleanor Williams Source NHS GMS was added to NFIX.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NF1 Eleanor Williams Source NHS GMS was added to NF1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NEU1 Eleanor Williams Source NHS GMS was added to NEU1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NEK1 Eleanor Williams Source NHS GMS was added to NEK1.
Skeletal dysplasia v1.145 NANS Eleanor Williams Source NHS GMS was added to NANS.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 NAGLU Eleanor Williams Source NHS GMS was added to NAGLU.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MYCN Eleanor Williams Source NHS GMS was added to MYCN.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MSX2 Eleanor Williams Source NHS GMS was added to MSX2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MPDU1 Eleanor Williams Source NHS GMS was added to MPDU1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MNX1 Eleanor Williams Source NHS GMS was added to MNX1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MMP9 Eleanor Williams Source NHS GMS was added to MMP9.
Skeletal dysplasia v1.145 MMP2 Eleanor Williams Source NHS GMS was added to MMP2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MMP13 Eleanor Williams Source NHS GMS was added to MMP13.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MKS1 Eleanor Williams Source NHS GMS was added to MKS1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MIR17HG Eleanor Williams Source NHS GMS was added to MIR17HG.
Skeletal dysplasia v1.145 MGP Eleanor Williams Source NHS GMS was added to MGP.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MESP2 Eleanor Williams Source NHS GMS was added to MESP2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MEOX1 Eleanor Williams Source NHS GMS was added to MEOX1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MEGF8 Eleanor Williams Source NHS GMS was added to MEGF8.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MATN3 Eleanor Williams Source NHS GMS was added to MATN3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Skeletal dysplasia v1.145 MASP1 Eleanor Williams gene: MASP1 was added
gene: MASP1 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: MASP1 was set to
Skeletal dysplasia v1.145 MAP3K7 Eleanor Williams Source NHS GMS was added to MAP3K7.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MAN2B1 Eleanor Williams Source NHS GMS was added to MAN2B1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 MAFB Eleanor Williams Source NHS GMS was added to MAFB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LTBP3 Eleanor Williams Source NHS GMS was added to LTBP3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LTBP2 Eleanor Williams gene: LTBP2 was added
gene: LTBP2 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: LTBP2 was set to
Skeletal dysplasia v1.145 LRP5 Eleanor Williams Source NHS GMS was added to LRP5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LRP4 Eleanor Williams Source NHS GMS was added to LRP4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LPIN2 Eleanor Williams Source NHS GMS was added to LPIN2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LONP1 Eleanor Williams Source NHS GMS was added to LONP1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LMX1B Eleanor Williams Source NHS GMS was added to LMX1B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LMNA Eleanor Williams Source NHS GMS was added to LMNA.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LMBR1 Eleanor Williams Source NHS GMS was added to LMBR1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LIFR Eleanor Williams Source NHS GMS was added to LIFR.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LFNG Eleanor Williams Source NHS GMS was added to LFNG.
Skeletal dysplasia v1.145 LEMD3 Eleanor Williams Source NHS GMS was added to LEMD3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 LBR Eleanor Williams Source NHS GMS was added to LBR.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 KMT2D Eleanor Williams gene: KMT2D was added
gene: KMT2D was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: KMT2D was set to
Skeletal dysplasia v1.145 KIF7 Eleanor Williams Source NHS GMS was added to KIF7.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 KIF22 Eleanor Williams Source NHS GMS was added to KIF22.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 KAT6B Eleanor Williams Source NHS GMS was added to KAT6B.
Skeletal dysplasia v1.145 KAT6A Eleanor Williams Source NHS GMS was added to KAT6A.
Skeletal dysplasia v1.145 INPPL1 Eleanor Williams Source NHS GMS was added to INPPL1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IMPAD1 Eleanor Williams Source NHS GMS was added to IMPAD1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IL1RN Eleanor Williams Source NHS GMS was added to IL1RN.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IL11RA Eleanor Williams Source NHS GMS was added to IL11RA.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IKBKG Eleanor Williams Source NHS GMS was added to IKBKG.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IHH Eleanor Williams Source NHS GMS was added to IHH.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IGF1R Eleanor Williams gene: IGF1R was added
gene: IGF1R was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: IGF1R was set to
Skeletal dysplasia v1.145 IFT81 Eleanor Williams Source NHS GMS was added to IFT81.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IFT80 Eleanor Williams Source NHS GMS was added to IFT80.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IFT52 Eleanor Williams Source NHS GMS was added to IFT52.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IFT43 Eleanor Williams Source NHS GMS was added to IFT43.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IFT172 Eleanor Williams Source NHS GMS was added to IFT172.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IFT140 Eleanor Williams Source NHS GMS was added to IFT140.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IFT122 Eleanor Williams Source NHS GMS was added to IFT122.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IFITM5 Eleanor Williams Source NHS GMS was added to IFITM5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IFIH1 Eleanor Williams gene: IFIH1 was added
gene: IFIH1 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: IFIH1 was set to
Skeletal dysplasia v1.145 IDUA Eleanor Williams Source NHS GMS was added to IDUA.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IDS Eleanor Williams Source NHS GMS was added to IDS.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 IDH2 Eleanor Williams Source NHS GMS was added to IDH2.
Skeletal dysplasia v1.145 IDH1 Eleanor Williams Source NHS GMS was added to IDH1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ICK Eleanor Williams Source NHS GMS was added to ICK.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 HSPG2 Eleanor Williams Source NHS GMS was added to HSPG2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 HPGD Eleanor Williams Source NHS GMS was added to HPGD.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 HOXD13 Eleanor Williams Source NHS GMS was added to HOXD13.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 HOXD11 Eleanor Williams gene: HOXD11 was added
gene: HOXD11 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: HOXD11 was set to
Skeletal dysplasia v1.145 HOXA13 Eleanor Williams Source NHS GMS was added to HOXA13.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 HOXA11 Eleanor Williams Source NHS GMS was added to HOXA11.
Skeletal dysplasia v1.145 HNRNPK Eleanor Williams Source NHS GMS was added to HNRNPK.
Skeletal dysplasia v1.145 HGSNAT Eleanor Williams Source NHS GMS was added to HGSNAT.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 HES7 Eleanor Williams Source NHS GMS was added to HES7.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 HDAC8 Eleanor Williams Source NHS GMS was added to HDAC8.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 HDAC4 Eleanor Williams Source NHS GMS was added to HDAC4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GZF1 Eleanor Williams Source NHS GMS was added to GZF1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GUSB Eleanor Williams Source NHS GMS was added to GUSB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GSC Eleanor Williams Source NHS GMS was added to GSC.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GPX4 Eleanor Williams Source NHS GMS was added to GPX4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GPC6 Eleanor Williams Source NHS GMS was added to GPC6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GORAB Eleanor Williams Source NHS GMS was added to GORAB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GNS Eleanor Williams Source NHS GMS was added to GNS.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GNPTG Eleanor Williams Source NHS GMS was added to GNPTG.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GNPTAB Eleanor Williams Source NHS GMS was added to GNPTAB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GNPAT Eleanor Williams Source NHS GMS was added to GNPAT.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GNAS Eleanor Williams Source NHS GMS was added to GNAS.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GLI3 Eleanor Williams Source NHS GMS was added to GLI3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GLB1 Eleanor Williams Source NHS GMS was added to GLB1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GJA1 Eleanor Williams Source NHS GMS was added to GJA1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GHR Eleanor Williams Source NHS GMS was added to GHR.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GDF6 Eleanor Williams Source NHS GMS was added to GDF6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GDF5 Eleanor Williams Source NHS GMS was added to GDF5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GDF3 Eleanor Williams gene: GDF3 was added
gene: GDF3 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: GDF3 was set to
Skeletal dysplasia v1.145 GALNT3 Eleanor Williams Source NHS GMS was added to GALNT3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 GALNS Eleanor Williams Source NHS GMS was added to GALNS.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FZD2 Eleanor Williams Source NHS GMS was added to FZD2.
Skeletal dysplasia v1.145 FUCA1 Eleanor Williams Source NHS GMS was added to FUCA1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FN1 Eleanor Williams gene: FN1 was added
gene: FN1 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: FN1 was set to
Skeletal dysplasia v1.145 FLNB Eleanor Williams Source NHS GMS was added to FLNB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FLNA Eleanor Williams Source NHS GMS was added to FLNA.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FKBP10 Eleanor Williams Source NHS GMS was added to FKBP10.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FIG4 Eleanor Williams Source NHS GMS was added to FIG4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FGFR3 Eleanor Williams Source NHS GMS was added to FGFR3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FGFR2 Eleanor Williams Source NHS GMS was added to FGFR2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FGFR1 Eleanor Williams Source NHS GMS was added to FGFR1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FGF9 Eleanor Williams Source NHS GMS was added to FGF9.
Skeletal dysplasia v1.145 FGF23 Eleanor Williams Source NHS GMS was added to FGF23.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FGF16 Eleanor Williams Source NHS GMS was added to FGF16.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FGF10 Eleanor Williams Source NHS GMS was added to FGF10.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FERMT3 Eleanor Williams Source NHS GMS was added to FERMT3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FBN2 Eleanor Williams Source NHS GMS was added to FBN2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FBN1 Eleanor Williams Source NHS GMS was added to FBN1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FBLN1 Eleanor Williams Source NHS GMS was added to FBLN1.
Skeletal dysplasia v1.145 FBLIM1 Eleanor Williams gene: FBLIM1 was added
gene: FBLIM1 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: FBLIM1 was set to
Skeletal dysplasia v1.145 FAM58A Eleanor Williams Source NHS GMS was added to FAM58A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FAM20C Eleanor Williams Source NHS GMS was added to FAM20C.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 FAM111A Eleanor Williams Source NHS GMS was added to FAM111A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EZH2 Eleanor Williams Source NHS GMS was added to EZH2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EXTL3 Eleanor Williams Source NHS GMS was added to EXTL3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EXT2 Eleanor Williams Source NHS GMS was added to EXT2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EXT1 Eleanor Williams Source NHS GMS was added to EXT1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EVC2 Eleanor Williams Source NHS GMS was added to EVC2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EVC Eleanor Williams Source NHS GMS was added to EVC.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ESCO2 Eleanor Williams Source NHS GMS was added to ESCO2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ERF Eleanor Williams Source NHS GMS was added to ERF.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EP300 Eleanor Williams Source NHS GMS was added to EP300.
Skeletal dysplasia v1.145 EOGT Eleanor Williams Source NHS GMS was added to EOGT.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ENPP1 Eleanor Williams Source NHS GMS was added to ENPP1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EIF2AK3 Eleanor Williams Source NHS GMS was added to EIF2AK3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EFTUD2 Eleanor Williams Source NHS GMS was added to EFTUD2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EFNB1 Eleanor Williams Source NHS GMS was added to EFNB1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EED Eleanor Williams Source NHS GMS was added to EED.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 EBP Eleanor Williams Source NHS GMS was added to EBP.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DYNC2LI1 Eleanor Williams Source NHS GMS was added to DYNC2LI1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DYNC2H1 Eleanor Williams Source NHS GMS was added to DYNC2H1.
Skeletal dysplasia v1.145 DYM Eleanor Williams Source NHS GMS was added to DYM.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DVL3 Eleanor Williams Source NHS GMS was added to DVL3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DVL1 Eleanor Williams Source NHS GMS was added to DVL1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DPM1 Eleanor Williams Source NHS GMS was added to DPM1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DOCK6 Eleanor Williams Source NHS GMS was added to DOCK6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DNMT3A Eleanor Williams Source NHS GMS was added to DNMT3A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DMP1 Eleanor Williams Source NHS GMS was added to DMP1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DLX6 Eleanor Williams Source NHS GMS was added to DLX6.
Skeletal dysplasia v1.145 DLX5 Eleanor Williams Source NHS GMS was added to DLX5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DLX3 Eleanor Williams Source NHS GMS was added to DLX3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DLL4 Eleanor Williams Source NHS GMS was added to DLL4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DLL3 Eleanor Williams Source NHS GMS was added to DLL3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DIS3L2 Eleanor Williams Source NHS GMS was added to DIS3L2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DHODH Eleanor Williams Source NHS GMS was added to DHODH.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DHCR24 Eleanor Williams Source NHS GMS was added to DHCR24.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DDR2 Eleanor Williams Source NHS GMS was added to DDR2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 DCC Eleanor Williams Source NHS GMS was added to DCC.
Skeletal dysplasia v1.145 CYP27B1 Eleanor Williams Source NHS GMS was added to CYP27B1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CUL7 Eleanor Williams Source NHS GMS was added to CUL7.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CTSK Eleanor Williams Source NHS GMS was added to CTSK.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CTSC Eleanor Williams Source NHS GMS was added to CTSC.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CTSA Eleanor Williams Source NHS GMS was added to CTSA.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CSPP1 Eleanor Williams Source NHS GMS was added to CSPP1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CRTAP Eleanor Williams Source NHS GMS was added to CRTAP.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CREBBP Eleanor Williams Source NHS GMS was added to CREBBP.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CREB3L1 Eleanor Williams Source NHS GMS was added to CREB3L1.
Skeletal dysplasia v1.145 COMP Eleanor Williams Source NHS GMS was added to COMP.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COLEC11 Eleanor Williams Source NHS GMS was added to COLEC11.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COLEC10 Eleanor Williams gene: COLEC10 was added
gene: COLEC10 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: COLEC10 was set to
Skeletal dysplasia v1.145 COL9A3 Eleanor Williams Source NHS GMS was added to COL9A3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COL9A2 Eleanor Williams Source NHS GMS was added to COL9A2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COL9A1 Eleanor Williams Source NHS GMS was added to COL9A1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COL2A1 Eleanor Williams Source NHS GMS was added to COL2A1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COL1A2 Eleanor Williams Source NHS GMS was added to COL1A2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COL1A1 Eleanor Williams Source NHS GMS was added to COL1A1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COL11A2 Eleanor Williams Source NHS GMS was added to COL11A2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COL11A1 Eleanor Williams Source NHS GMS was added to COL11A1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COL10A1 Eleanor Williams Source NHS GMS was added to COL10A1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 COG1 Eleanor Williams Source NHS GMS was added to COG1.
Skeletal dysplasia v1.145 CLCN7 Eleanor Williams Source NHS GMS was added to CLCN7.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CLCN5 Eleanor Williams Source NHS GMS was added to CLCN5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CKAP2L Eleanor Williams gene: CKAP2L was added
gene: CKAP2L was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: CKAP2L was set to
Skeletal dysplasia v1.145 CHSY1 Eleanor Williams Source NHS GMS was added to CHSY1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CHST3 Eleanor Williams Source NHS GMS was added to CHST3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CHST14 Eleanor Williams Source NHS GMS was added to CHST14.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 C21orf2 Eleanor Williams Source NHS GMS was added to C21orf2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CEP290 Eleanor Williams Source NHS GMS was added to CEP290.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CEP120 Eleanor Williams Source NHS GMS was added to CEP120.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CDT1 Eleanor Williams Source NHS GMS was added to CDT1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CDKN1C Eleanor Williams Source NHS GMS was added to CDKN1C.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CDH3 Eleanor Williams Source NHS GMS was added to CDH3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CDC45 Eleanor Williams Source NHS GMS was added to CDC45.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CD96 Eleanor Williams gene: CD96 was added
gene: CD96 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: CD96 was set to
Skeletal dysplasia v1.145 CCDC8 Eleanor Williams Source NHS GMS was added to CCDC8.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CC2D2A Eleanor Williams Source NHS GMS was added to CC2D2A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CASR Eleanor Williams Source NHS GMS was added to CASR.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CANT1 Eleanor Williams Source NHS GMS was added to CANT1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 CA2 Eleanor Williams Source NHS GMS was added to CA2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 C2CD3 Eleanor Williams Source NHS GMS was added to C2CD3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 BMPR1B Eleanor Williams Source NHS GMS was added to BMPR1B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 BMPER Eleanor Williams Source NHS GMS was added to BMPER.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 BMP2 Eleanor Williams Source NHS GMS was added to BMP2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 BMP1 Eleanor Williams Source NHS GMS was added to BMP1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 BHLHA9 Eleanor Williams Source NHS GMS was added to BHLHA9.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 B9D1 Eleanor Williams Source NHS GMS was added to B9D1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 B4GALT7 Eleanor Williams Source NHS GMS was added to B4GALT7.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 B3GAT3 Eleanor Williams Source NHS GMS was added to B3GAT3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 B3GALT6 Eleanor Williams Source NHS GMS was added to B3GALT6.
Rating Changed from Green List (high evidence) to Green List (high evidence)