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Limb disorders v1.58 EIF4A3 Eleanor Williams commented on gene: EIF4A3: Associated with Robin sequence with cleft mandible and limb anomalies (#268305) in OMIM and RICHIERI-COSTA-PEREIRA SYNDROME in Gene2Phenotype (confirmed, 5_prime or 3_prime UTR mutation).

PMID: 24360810 - Favaro et al. 2014 - found in Brazilian families with RCPS 17 affected probands were homozygous for the 16-repeat allele in the 5 prime UTR of EIF4A3, and 3 apparently unrelated affected individuals were compound heterozygotes (15 or 16 repeats). All tested parents were heterozygous for the 16-repeat allele, and unaffected siblings either lacked the expanded allele or were heterozygotes. The 15- and 16-repeat allele haplotypes spanning EIF4A3 are consistent with a common origin and corroborate their previous founder effect hypothesis for most Brazilian RCPS-affected individuals. Sequencing of EIF4A3 in five additional Brazilian affected individuals ascertained elsewhererevealed that four of them (, including 2 siblings) were homozygous for the 16-repeat allele. In contrast, the fifth (individual 25) was a compound heterozygote, possessing a 14-repeat allele in trans with a nucleotide change, c.809A>G, p.Asp270Gly. the c.809A>G mutation is embedded in a distinct haplotype, suggesting multiple pathogenic mutational origins in EIF4A3.
EIF4A3 transcript abundance was about 30%–40% lower in affected individuals than in controls in both cell types tested.
Zebrafish morpholinos show underdevelopment of craniofacial cartilage, bone alterations, and clefting of the lower jaw.
Limb disorders v1.58 NCAPG2 Eleanor Williams Classified gene: NCAPG2 as Amber List (moderate evidence)
Limb disorders v1.58 NCAPG2 Eleanor Williams Added comment: Comment on list classification: 2 cases. Zebra fish model does not show limb phenotype.
Limb disorders v1.58 NCAPG2 Eleanor Williams Gene: ncapg2 has been classified as Amber List (Moderate Evidence).
Limb disorders v1.57 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)
Limb disorders v1.57 LBR Eleanor Williams Mode of inheritance for gene: LBR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v1.56 EPHA4 Eleanor Williams commented on gene: EPHA4: EPHA4 not associated with any phenotype in OMIM or Gene2Phenotype.

PMID: 25959774 - Lupiáñez et al 2015 - studied limb abnormalities in 3 sets of families:
Group 1 - 3 unrelated families with a dominantly inherited novel type of brachydactyly, characterized by short digits predominantly on the preaxial (radial) side resulting in stub thumbs, short index fingers and a cutaneous web between the first and second fingers. aCGH revealed heterozygous deletions of 1.75–1.9 Mb on chromosome 2q35–36 in all three affected families. All three deletions include the EPHA4 gene along with a large portion of its surrounding TAD and extend into the non-coding part of the adjacent PAX3 TAD (topologically associated domain), thereby removing the predicted boundary between the EPHA4 and PAX3 TADs. Mutant mice with a deletion corresponding to the human disease alleles recapitulated the phenotype observed in patients.
Group 2 - 2 unrelated families with F-syndrome, a limb malformation syndrome characterized by severe and complex syndactyly, often involving the first and second fingers, and polydactyly of the feet. By whole genome sequencing they detected a ~1.1 Mb heterozygous inversion in family F1 and a ~1.4 Mb heterozygous duplication, arranged in direct tandem orientation, in family F2. The telomeric breakpoints were located 1.4 Mb away from the EPHA4 gene within the gene desert in the case of the inversion, and 1.2 Mb in the case of the duplication. Heterozygous as well as homozygous newborn mice generated via tetraploid aggregation died shortly after birth of unknown cause and did not show overt limb phenotypes or other morphological defects
Group 3 - a family that carries a heterozygous ~900 kb duplication in chromosomal region 2q35 that results in severe polysyndactyly and craniofacial abnormalities. The phenotype is reminiscent of the doublefoot (Dbf) mouse mutant, which also features massive polysyndactyly and was shown to be caused by a ~600 kb deletion affecting the same region (Babbs et al., 2008)
Using 4C-seq they show that In wild-type distal limbs, there was minimal interaction of Pax3, Wnt6 and Ihh with non-coding sequences in the Epha4 TAD. In contrast, all three genes showed substantial interaction with the Epha4 TAD in the mutants. Similar results were found using patient fibroblasts.

Genomic re-arrangements in the Epha4 TAD can result in limb abnormalities. It maybe best to represent these as regions of gain or loss in PanelApp
Limb disorders v1.56 SOX9 Eleanor Williams commented on gene: SOX9: Associated with Campomelic dysplasia (114290) in OMIM and CAMPOMELIC DYSPLASIA and PIERRE ROBIN SEQUENCE in Gene2Phenotype (both confirmed).

Publications relating to the duplications in the region between KCNJ2 and SOX9:

PMID: 19639023 - Kurth et al 2009 - investigated four families with symmetric brachydactyly of the hands and feet as well as hyponychia or anonychia. All affected were of normal height and had no other skeletal abnormality. They identified overlapping duplications in a ∼2 Mb interval on chromosome 17q24.3. Comparison of the four duplications revealed a minimal critical region of ∼1.2 Mb encompassing a large gene desert between KCNJ2 and SOX9. In situ hybridizations in mouse embryos, showed that Sox9 was strongly expressed in the distal mesenchymal condensations at embryonic day (E) 12.5 that will later develop into the terminal phalanges and, at a later time point (E17.5), in the anlagen of the developing claw.

PMID: 27706140 - Franke et al 2016 - used chromosome conformation capture methods to look at topologically associated domains in patient cells and mouse models where the regulatory region next to SOX9 is duplicated. They generated mice with a duplicated region associated with Cooks syndrome as reported by Kurth et al 2009 (which they call Dup-C). cHi-C of E12.5 Dup-C limb buds showed a new chromatin domain corresponding to the duplicated region.
RNA sequencing expression analysis of Dup-C limb buds at E12.5 and E17.5 confirmed the upregulation of Kcnj2, whereas other genes around the locus stayed unchanged, in particular Sox9, but also Kcnj16. Thus, the inclusion of Kcnj2 in the neo-TAD resulted in its activation by regulatory elements that originally belonged to the Sox9 TAD.


Other publications.
PMID: 21373255 - Corbani et al 2011 - reported patient with SOX9 missense mutation and mild form of campomelic dysplasia. Features include short stature, dysmorphic facial features, limitation of supination and pronation of the forearms, dysplastic nails, and bone abnormalities consisting especially of cone-shaped epiphyses of the middle phalanx of the 2nd fingers, brachydactyly and clinodactyly of the middle phalanx of both 5th fingers, short 4th metacarpals, radial and femoral head subluxation, hypoplastic scapulae, humeral and ulnar epiphyseal abnormalities, unossified symphysis pubis, and a significant delay in bone age.

PMID: 24704791 - Takenouchi et al 2014 - report patient with many features of the type 2 collagen disorder including micrognathia, cleft palate, flat midface, and visual and hearing impairment, and a retarded enchondral ossification of the appendicular skeleton during the infantile period. The patient had in addition severe developmental delay. A de novo heterozygous missense mutation, c.239T>G p.Val80Gly, in exon 1 of SOX9 was found.

Summary:
Evidence that duplication of a region upstream of SOX9 can result in a brachydactyly phenotype. This appears to be as a result of increased expression of KCNJ2. It maybe most appropriate to add this upstream region as a CNV.
Limb disorders v1.56 SMAD6 Eleanor Williams commented on gene: SMAD6: Added Incomplete penetrance as Yang et al 2019 found only 20% penetrance for LOF variant carriers.
Limb disorders v1.56 SMAD6 Eleanor Williams Penetrance for gene SMAD6 was set from to None
Limb disorders v1.55 SMAD6 Eleanor Williams Publications for gene: SMAD6 were set to
Limb disorders v1.54 SMAD6 Eleanor Williams Phenotypes for gene: SMAD6 were changed from radioulnar synostosis to radioulnar synostosis
Limb disorders v1.54 SMAD6 Eleanor Williams Phenotypes for gene: SMAD6 were changed from to radioulnar synostosis
Limb disorders v1.53 SMAD6 Eleanor Williams changed review comment from: Not associated with radioulnar synostosis in OMIM or Gene2Phenotype, although is associated with susceptibility to craniosynostosis and Aortic valve disease 2.

PMID: 31138930 - Yang et al 2019 - investigated 140 sporadic patients and 11 families with RUS of an unknown cause. Potentially disease causing variants were found in SMAD6 in 30 individuals from 27 families. In 22 individuals the variants were detected by whole exome sequencing and confirmed by Sanger sequencing. In the remaining 8 individuals targetting sequencing of SMAD6 using Sanger sequencing was performed. 27 different variants were identified (19 LOF and 8 missense), in 24 sporadic patients and three families. Parental genomic DNA was available for 11 probands with SMAD6 rare variants. Sanger sequencing validated that four variants were de novo, six were inherited from the probands’ unaffected mother, and one was inherited from the probands’ unaffected father.
Reduced penetrance was found - after excluding the index cases, the found 2/10 SMAD6- LOF carriers have nsRUS. Therefore, the penetrance of RUS in SMAD6-LOF cases is reduced (~20%).
No significant associations were observed between BMP2-Chr20–7106289T-C genotype and nsRUS in cases with SMAD6 rare variants.; to: Not associated with radioulnar synostosis in OMIM or Gene2Phenotype, although is associated with susceptibility to craniosynostosis and Aortic valve disease 2.

PMID: 31138930 - Yang et al 2019 - investigated 140 sporadic patients and 11 families with Radioulnar synostosis (RUS) of an unknown cause. Potentially disease causing variants were found in SMAD6 in 30 individuals from 27 families. In 22 individuals the variants were detected by whole exome sequencing and confirmed by Sanger sequencing. In the remaining 8 individuals targeted Sanger sequencing of SMAD6 was performed. 27 different variants were identified (19 LOF and 8 missense), in 24 sporadic patients and three families. Parental genomic DNA was available for 11 probands with SMAD6 rare variants. Sanger sequencing validated that four variants were de novo, six were inherited from the probands’ unaffected mother, and one was inherited from the probands’ unaffected father.
Reduced penetrance was found - after excluding the index cases, the found 2/10 SMAD6- LOF carriers have nsRUS. Therefore, the penetrance of RUS in SMAD6-LOF cases is reduced (~20%).
No significant associations were observed between BMP2-Chr20–7106289T-C genotype and nsRUS in cases with SMAD6 rare variants.
Limb disorders v1.53 SMAD6 Eleanor Williams commented on gene: SMAD6: Not associated with radioulnar synostosis in OMIM or Gene2Phenotype, although is associated with susceptibility to craniosynostosis and Aortic valve disease 2.

PMID: 31138930 - Yang et al 2019 - investigated 140 sporadic patients and 11 families with RUS of an unknown cause. Potentially disease causing variants were found in SMAD6 in 30 individuals from 27 families. In 22 individuals the variants were detected by whole exome sequencing and confirmed by Sanger sequencing. In the remaining 8 individuals targetting sequencing of SMAD6 using Sanger sequencing was performed. 27 different variants were identified (19 LOF and 8 missense), in 24 sporadic patients and three families. Parental genomic DNA was available for 11 probands with SMAD6 rare variants. Sanger sequencing validated that four variants were de novo, six were inherited from the probands’ unaffected mother, and one was inherited from the probands’ unaffected father.
Reduced penetrance was found - after excluding the index cases, the found 2/10 SMAD6- LOF carriers have nsRUS. Therefore, the penetrance of RUS in SMAD6-LOF cases is reduced (~20%).
No significant associations were observed between BMP2-Chr20–7106289T-C genotype and nsRUS in cases with SMAD6 rare variants.
Limb disorders v1.53 FAM92A Eleanor Williams Classified gene: FAM92A as Amber List (moderate evidence)
Limb disorders v1.53 FAM92A Eleanor Williams Added comment: Comment on list classification: Promoted from red to amber. 1 case plus a mouse knockout showing a similar phenotype.
Limb disorders v1.53 FAM92A Eleanor Williams Gene: fam92a has been classified as Amber List (Moderate Evidence).
Limb disorders v1.52 FAM92A Eleanor Williams commented on gene: FAM92A: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM.

PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with
autosomal recessive nonsyndromic postaxial polydactyly type A. Blood was taken from 3 affected and 3 non-affected idividuals. DNA from one child was used for exome sequencing and revealed a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene. Sanger sequencing confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. It is predicted to be targeted by the classical nonsense-mediated decay pathway. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri.


we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype.

In 3 Pakistani brothers with postaxial polydactyly type A9 (PAPA9; 618219), identified homozygosity for a nonsense mutation in the FAM92A gene (R160X; 617273.0001) that segregated with disease and was not found in 186 Pakistani controls.


▼ Animal Model
Schrauwen et al. (2018) generated Fam92a -/- mice and observed extra bone growth or exostosis on the deltoid tuberosity of the humerus, consistent with tendon calcification. Abnormal digit morphology was significantly enriched in the mutant mice compared to controls, and included polysyndactyly and osteomas
Limb disorders v1.52 GLI1 Eleanor Williams Publications for gene: GLI1 were set to 28973407; 28973407
Limb disorders v1.51 GLI1 Eleanor Williams Phenotypes for gene: GLI1 were changed from Polydactyly, postaxial, type A8, 618123); Polydactyly, preaxial I, 174400 to Polydactyly, postaxial, type A8, 618123; Polydactyly, preaxial I, 174400
Limb disorders v1.50 GLI1 Eleanor Williams Phenotypes for gene: GLI1 were changed from to Polydactyly, postaxial, type A8, 618123); Polydactyly, preaxial I, 174400
Limb disorders v1.49 GLI1 Eleanor Williams changed review comment from: Comment on list classification: >3 cases of variants in GLI1 in families with polydactyly; to: Comment on list classification: Changing rating from red to green. >3 cases of variants in GLI1 in families with polydactyly
Limb disorders v1.49 GLI1 Eleanor Williams Classified gene: GLI1 as Green List (high evidence)
Limb disorders v1.49 GLI1 Eleanor Williams Added comment: Comment on list classification: >3 cases of variants in GLI1 in families with polydactyly
Limb disorders v1.49 GLI1 Eleanor Williams Gene: gli1 has been classified as Green List (High Evidence).
Limb disorders v1.48 GLI1 Eleanor Williams changed review comment from: Associated with Polydactyly, postaxial, type A8 (#618123) and Polydactyly, preaxial I (#174400) in OMIM.

Postaxial Polydactyly Type A8:
PMID: 28973407 - Palencia-Campos et al. 2017- 3 cases. They report data from 3 families, 2 Turkish (1 consangineous),1 Pakistani (consangineous) with developmental defects overlapping with Ellis–van Creveld syndrome, including postaxial polydactyly of the hands and/or feet . Homozygous truncating mutations (NM_005269.2: c.2340G > A; p.Trp780*, NM_005269.2: c.1930C > T; p.Gln644*, NM_005269.2: c.337C > T; p.Arg113*) were identified in patients in all 3 families.
Note, in the extended members of family 1, one individual is reported with polydactyly but is heterozygous for the p.Trp780* variant and one individual with polydactyly but no p.Trp780* variant is reported (possible different homozygous genetic alteration not detectable by exome sequencing?).

Polydactyly, preaxial I:
PMID: 30620395 - Ullah et al. 2019 - 1 case. Pakistani family segregating autosomal recessive form of pre‐axial polydactyly. 2 individuals from two parts of the family were sequenced and a novel homozygous missense mutation identified c.1517T>A; p.Leu506Gln) in the GLI1. The variant segregated with the disease phenotype in the family.
It was not found in their in‐house exome sequence data from 70 additional unrelated Pakistani individuals with normal limb phenotypes but was found in heterozygous state in the gnomAD browser, with an allele frequency of 0.0002109, but not in homozygous state.; to: Associated with Polydactyly, postaxial, type A8 (#618123) and Polydactyly, preaxial I (#174400) in OMIM.

Postaxial Polydactyly Type A8:
PMID: 28973407 - Palencia-Campos et al. 2017- 3 cases. They report data from 3 families, 2 Turkish (1 consangineous),1 Pakistani (consangineous) with developmental defects overlapping with Ellis–van Creveld syndrome, including postaxial polydactyly of the hands and/or feet . Homozygous truncating mutations (NM_005269.2: c.2340G > A; p.Trp780*, NM_005269.2: c.1930C > T; p.Gln644*, NM_005269.2: c.337C > T; p.Arg113*) were identified in patients in all 3 families.
Note, in the extended members of family 1, one individual is reported with polydactyly but is heterozygous for the p.Trp780* variant (patient 3) and one individual with polydactyly but no p.Trp780* variant is reported (patient 4). Homozygosity mapping suggests that these results were consistent with GLI1-W780X being responsible for the phenotype of patients 1–2 and a different genetic variation or disease mechanism for the phenotypes of patients 3 and 4.

Polydactyly, preaxial I:
PMID: 30620395 - Ullah et al. 2019 - 1 case. Pakistani family segregating autosomal recessive form of pre‐axial polydactyly. 2 individuals from two parts of the family were sequenced and a novel homozygous missense mutation identified c.1517T>A; p.Leu506Gln) in the GLI1. The variant segregated with the disease phenotype in the family. It was not found in their in‐house exome sequence data from 70 additional unrelated Pakistani individuals with normal limb phenotypes but was found in heterozygous state in the gnomAD browser, with an allele frequency of 0.0002109, but not in homozygous state.
Limb disorders v1.48 GLI1 Eleanor Williams commented on gene: GLI1: Associated with Polydactyly, postaxial, type A8 (#618123) and Polydactyly, preaxial I (#174400) in OMIM.

Postaxial Polydactyly Type A8:
PMID: 28973407 - Palencia-Campos et al. 2017- 3 cases. They report data from 3 families, 2 Turkish (1 consangineous),1 Pakistani (consangineous) with developmental defects overlapping with Ellis–van Creveld syndrome, including postaxial polydactyly of the hands and/or feet . Homozygous truncating mutations (NM_005269.2: c.2340G > A; p.Trp780*, NM_005269.2: c.1930C > T; p.Gln644*, NM_005269.2: c.337C > T; p.Arg113*) were identified in patients in all 3 families.
Note, in the extended members of family 1, one individual is reported with polydactyly but is heterozygous for the p.Trp780* variant and one individual with polydactyly but no p.Trp780* variant is reported (possible different homozygous genetic alteration not detectable by exome sequencing?).

Polydactyly, preaxial I:
PMID: 30620395 - Ullah et al. 2019 - 1 case. Pakistani family segregating autosomal recessive form of pre‐axial polydactyly. 2 individuals from two parts of the family were sequenced and a novel homozygous missense mutation identified c.1517T>A; p.Leu506Gln) in the GLI1. The variant segregated with the disease phenotype in the family.
It was not found in their in‐house exome sequence data from 70 additional unrelated Pakistani individuals with normal limb phenotypes but was found in heterozygous state in the gnomAD browser, with an allele frequency of 0.0002109, but not in homozygous state.
Limb disorders v1.48 STKLD1 Eleanor Williams Classified gene: STKLD1 as Amber List (moderate evidence)
Limb disorders v1.48 STKLD1 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. 2 cases which appear to be from unrelated families although the same variant was found.
Limb disorders v1.48 STKLD1 Eleanor Williams Gene: stkld1 has been classified as Amber List (Moderate Evidence).
Limb disorders v1.47 FAM92A Eleanor Williams gene: FAM92A was added
gene: FAM92A was added to Limb disorders. Sources: Literature
Mode of inheritance for gene: FAM92A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM92A were set to 30395363
Phenotypes for gene: FAM92A were set to postaxial polydactyly type A9
Review for gene: FAM92A was set to AMBER
Added comment: Sources: Literature
Limb disorders v1.46 GLI1 Eleanor Williams gene: GLI1 was added
gene: GLI1 was added to Limb disorders. Sources: Literature
Mode of inheritance for gene: GLI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLI1 were set to 28973407; 28973407
Review for gene: GLI1 was set to AMBER
Added comment: Gene listed in Table 1 in PMID: 30945277 as associated with polydactyly.
Sources: Literature
Limb disorders v1.45 STKLD1 Eleanor Williams changed review comment from: This gene is not in OMIM or Gene2Phenotype.

PMID: 30945277 - Umair et al 2019 - 2 consanguineous families of Pakistani origin segregating non‐syndromic pre‐axial polydactyly in autosomal recessive manner. The families originated from two different parts of Pakistan. Whole exome sequencing was used to identify the same homozygous variant c.84C > A, p.Tyr28* in both families that segregated with the condition. 2 affected and 5 unaffected family members were analysed. The variant was not found in homozygous state in ExAC, gnomAD, internal database, 1000 Genomes, EVS, dbSNP, and predicted to be damaging in online available tools used for bioinformatics analysis. However, a minor allele frequency of 0.001119 for the variant was noted in the South Asian population.; to: This gene is not in OMIM or Gene2Phenotype.

PMID: 30945277 - Umair et al 2019 - 2 consanguineous families of Pakistani origin segregating non‐syndromic pre‐axial polydactyly in autosomal recessive manner. The families originated from two different parts of Pakistan. Whole exome sequencing was used to identify the same homozygous variant c.84C > A, p.Tyr28* (NM_153710.3) in both families that segregated with the condition. 2 affected and 5 unaffected family members were analysed. The variant was not found in homozygous state in ExAC, gnomAD, internal database, 1000 Genomes, EVS, dbSNP, and predicted to be damaging in online available tools used for bioinformatics analysis. However, a minor allele frequency of 0.001119 for the variant was noted in the South Asian population.

The transcript mentioned in this paper NM_153710.3 is linked to GeneID:169436, HGNC:28669 which is STKLD1 (previous name C9orf96).
Limb disorders v1.45 STKLD1 Eleanor Williams changed review comment from: This gene is not in OMIM or Gene2Phenotype.

PMID: 30945277 - Umair et al 2019 - 2 consanguineous families of Pakistani origin segregating non‐syndromic pre‐axial polydactyly in autosomal recessive manner. The families originated from two different parts of Pakistan. Whole exome sequencing was used to identify the same variant c.84C > A, p.Tyr28* in both families. 4 affected and 10 unaffected family members were analysed. The variant was not found in homozygous state in ExAC, gnomAD, internal database, 1000 Genomes, EVS, dbSNP, and predicted to be damaging in online available tools used for bioinformatics analysis. However, a minor allele frequency of 0.001119 for the variant was noted in the South Asian population.; to: This gene is not in OMIM or Gene2Phenotype.

PMID: 30945277 - Umair et al 2019 - 2 consanguineous families of Pakistani origin segregating non‐syndromic pre‐axial polydactyly in autosomal recessive manner. The families originated from two different parts of Pakistan. Whole exome sequencing was used to identify the same homozygous variant c.84C > A, p.Tyr28* in both families that segregated with the condition. 2 affected and 5 unaffected family members were analysed. The variant was not found in homozygous state in ExAC, gnomAD, internal database, 1000 Genomes, EVS, dbSNP, and predicted to be damaging in online available tools used for bioinformatics analysis. However, a minor allele frequency of 0.001119 for the variant was noted in the South Asian population.
Limb disorders v1.45 STKLD1 Eleanor Williams commented on gene: STKLD1: This gene is not in OMIM or Gene2Phenotype.

PMID: 30945277 - Umair et al 2019 - 2 consanguineous families of Pakistani origin segregating non‐syndromic pre‐axial polydactyly in autosomal recessive manner. The families originated from two different parts of Pakistan. Whole exome sequencing was used to identify the same variant c.84C > A, p.Tyr28* in both families. 4 affected and 10 unaffected family members were analysed. The variant was not found in homozygous state in ExAC, gnomAD, internal database, 1000 Genomes, EVS, dbSNP, and predicted to be damaging in online available tools used for bioinformatics analysis. However, a minor allele frequency of 0.001119 for the variant was noted in the South Asian population.
Limb disorders v1.45 GLI3 Eleanor Williams Publications for gene: GLI3 were set to
Limb disorders v1.44 GLI3 Eleanor Williams commented on gene: GLI3: PMID: 31115189 - Umair et al 2019 - report a five generation Pakastani kindred having 12 affected individuals exhibiting nonsyndromic postaxial polydactyly type A condition. Using exome sequencing in the three affected individuals, they identified a novel heterozygous frameshift variant (c.3567_3568insG; p.Ala1190Glyfs*57) in the transcriptional activator (TA2) domain of GLI3. The variant segregates with the disease phenotype in all members of the family. The variant was not observed in the ExAC browser, gnomAD, 1,000 Genomes, Pakistan Genetic Mutation database (Qasim et al., 2018) and in 135 in‐house exomes (Pakistani exomes).
Limb disorders v1.44 POLR1A Eleanor Williams commented on gene: POLR1A: Associated with Acrofacial dysostosis, Cincinnati type (#616462) in OMIM and Gene2Phenotype (probable).

PMID: 25913037 - Weaver et al. 2015 - report 3 individuals with mandibulofacial dysostosis, 2 of which have limb anomalies. All have putative pathogenic variants in POLR1A. Limb anomalies include short stature with congenital short bowed femurs with metaphyseal flaring, dysplastic acetabulae, and delayed or absent ossification of the capital femoral epiphyses in Individual 1A1, and short, broad fingers and toes in individual 1A3. polr1a mutant zebrafish exhibited cranioskeletal anomalies mimicking the human phenotype.
Limb disorders v1.44 GZF1 Eleanor Williams Publications for gene: GZF1 were set to
Limb disorders v1.43 GZF1 Eleanor Williams Phenotypes for gene: GZF1 were changed from to Joint laxity, short stature, and myopia, 617662; Larsen syndrome
Limb disorders v1.42 GZF1 Eleanor Williams changed review comment from: Associated with Joint laxity, short stature, and myopia (#617662) in OMIM and Larsen syndrome (probable) 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.; to: Associated with Joint laxity, short stature, and myopia (#617662) in OMIM and Larsen syndrome (probable) 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 and bilateral talipes equinovarus deformity. A homozygous truncating variant in GZF1 was identified (c.865G>T (pGlu289∗). Family 2 - another multiplex consanguineous Saudi family affected by severe myopia, retinal detachment, and milder skeletal involvement (generalized joint laxity). 1 family member had bilateral talipes. 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.
Limb disorders v1.42 GZF1 Eleanor Williams commented on gene: GZF1: Associated with Joint laxity, short stature, and myopia (#617662) in OMIM and Larsen syndrome (probable) 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.
Limb disorders v1.42 SUFU Eleanor Williams Publications for gene: SUFU were set to
Limb disorders v1.41 SUFU Eleanor Williams Phenotypes for gene: SUFU were changed from Joubert syndrome 32, 617757); Joubert Syndrome with Cranio-facial and Skeletal Defects to Joubert syndrome 32, 617757; Joubert Syndrome with Cranio-facial and Skeletal Defects
Limb disorders v1.40 SUFU Eleanor Williams Phenotypes for gene: SUFU were changed from to Joubert syndrome 32, 617757); Joubert Syndrome with Cranio-facial and Skeletal Defects
Limb disorders v1.39 SUFU Eleanor Williams commented on gene: SUFU: Associated with Joubert syndrome 32 (#617757) in OMIM and Joubert Syndrome with Cranio-facial and Skeletal Defects in Gene2Phenotype (probable).

PMID: 28965847 - Mori et al 2017 - 2 cases. They report four children from two unrelated consanguineous families (from Italy and Egypt) carrying homozygous missense variants (c.1217T>C,p.Ile406Thr and c.1218C>G,p.Ile406Met) in SUFU. The children presented with congenital ataxia and cerebellar vermis hypoplasia with elongated superior cerebellar peduncles (mild "molar tooth sign"), typical cranio-facial dysmorphisms (hypertelorism, depressed nasal bridge, frontal bossing), and 3 had postaxial polydactyly.
In family 1, the two affected siblings also had a homozygous missense variant in CDHR1 but is expressed only in the outer nuclear layer of the retina and pathogenic variants of this gene are known to cause an autosomal-recessive form of cone-rod dystrophy with onset in the late second decade of life (older than the probands).
Functional studies on fibroblasts and cell lines showed that the mutant proteins were less stable and more rapidly degraded than SUFU WT and had impaired ability to bind GLI3 and promote its cleavage into the repressor form GLI3R, while they maintained unaltered ability to bind GLI1. These findings suggest that both variants are hypomorphic alleles, resulting only in a partial loss of the normal gene function.
Limb disorders v1.39 TRAF7 Eleanor Williams Publications for gene: TRAF7 were set to
Limb disorders v1.38 TRAF7 Eleanor Williams Phenotypes for gene: TRAF7 were changed from to Cardiac, facial, and digital anomalies with developmental delay, 618164; Developmental Delay, Congenital Anomalies, and Dysmorphic Features
Limb disorders v1.37 TRAF7 Eleanor Williams changed review comment from: Associated with Cardiac, facial, and digital anomalies with developmental delay (#618164) in OMIM and Developmental Delay, Congenital Anomalies, and Dysmorphic Features in Gene2Phenotype.

PMID: 29961569 - Tokita et al. 2018 - 7 cases. They report missense variants in TRAF7 in seven unrelated individuals referred for clinical exome sequencing. There was substantial phenotypic overlap between individuals, with developmental delay, congenital heart defects, limb and digital anomalies, and dysmorphic features as key features. 6 individuals had de novo variants (absence of paternal DNA in one patient did not allow confirmation of a de novo variant), with four distinct missense changes, including a c.1964G>A (p.Arg655Gln) variant in 4 individuals. The variants affect evolutionarily conserved amino acids and are located in key functional domains.

All 7 subjects had limb and digital anomalies to a variable degree, including variant palmar/digital crease patterns (n = 6) and overlapping toes (n = 5) and clinodactyly (n=3). One subject (Subject 3) had more extensive involvement of the musculoskeletal system including scoliosis with degenerative joint disease, an asymmetric sternum, bilateral avascular necrosis of the hip, tibial malformation, valgus deformity of the ankles, flexion contractures of the hands, and subluxation of multiple joints in the hands and feet.; to: Associated with Cardiac, facial, and digital anomalies with developmental delay (#618164) in OMIM and Developmental Delay, Congenital Anomalies, and Dysmorphic Features in Gene2Phenotype.

PMID: 29961569 - Tokita et al. 2018 - 7 cases. They report missense variants in TRAF7 in seven unrelated individuals referred for clinical exome sequencing. There was substantial phenotypic overlap between individuals, with developmental delay, congenital heart defects, limb and digital anomalies, and dysmorphic features as key features. 6 individuals had de novo variants (absence of paternal DNA in one patient did not allow confirmation of a de novo variant), with four distinct missense changes, including a c.1964G>A (p.Arg655Gln) variant in 4 individuals. The variants affect evolutionarily conserved amino acids and are located in key functional domains.
All 7 subjects had limb and digital anomalies to a variable degree, including variant palmar/digital crease patterns (n = 6) and overlapping toes (n = 5) and clinodactyly (n=3). One subject (Subject 3) had more extensive involvement of the musculoskeletal system including scoliosis with degenerative joint disease, an asymmetric sternum, bilateral avascular necrosis of the hip, tibial malformation, valgus deformity of the ankles, flexion contractures of the hands, and subluxation of multiple joints in the hands and feet.
Limb disorders v1.37 TRAF7 Eleanor Williams changed review comment from: Associated with Cardiac, facial, and digital anomalies with developmental delay (#618164) in OMIM and Developmental Delay, Congenital Anomalies, and Dysmorphic Features in Gene2Phenotype.; to: Associated with Cardiac, facial, and digital anomalies with developmental delay (#618164) in OMIM and Developmental Delay, Congenital Anomalies, and Dysmorphic Features in Gene2Phenotype.

PMID: 29961569 - Tokita et al. 2018 - 7 cases. They report missense variants in TRAF7 in seven unrelated individuals referred for clinical exome sequencing. There was substantial phenotypic overlap between individuals, with developmental delay, congenital heart defects, limb and digital anomalies, and dysmorphic features as key features. 6 individuals had de novo variants (absence of paternal DNA in one patient did not allow confirmation of a de novo variant), with four distinct missense changes, including a c.1964G>A (p.Arg655Gln) variant in 4 individuals. The variants affect evolutionarily conserved amino acids and are located in key functional domains.

All 7 subjects had limb and digital anomalies to a variable degree, including variant palmar/digital crease patterns (n = 6) and overlapping toes (n = 5) and clinodactyly (n=3). One subject (Subject 3) had more extensive involvement of the musculoskeletal system including scoliosis with degenerative joint disease, an asymmetric sternum, bilateral avascular necrosis of the hip, tibial malformation, valgus deformity of the ankles, flexion contractures of the hands, and subluxation of multiple joints in the hands and feet.
Limb disorders v1.37 NCAPG2 Eleanor Williams Phenotypes for gene: NCAPG2 were changed from to Khan-Khan-Katsanis syndrome, 618460
Limb disorders v1.36 NCAPG2 Eleanor Williams Publications for gene: NCAPG2 were set to
Limb disorders v1.35 TRAF7 Eleanor Williams commented on gene: TRAF7: Associated with Cardiac, facial, and digital anomalies with developmental delay (#618164) in OMIM and Developmental Delay, Congenital Anomalies, and Dysmorphic Features in Gene2Phenotype.
Limb disorders v1.35 NCAPG2 Eleanor Williams changed review comment from: Associated with Khan-Khan-Katsanis syndrome (#618460) in OMIM.

PMID: 30609410 - Khan et al. 2019 - 2 unrelated cases with homozygous or compound heterozygous variants in NCAPG2.
Family 1 - female with bilateral postaxial polydactyly on the feet, moderate intellectual disability, ocular anomalies, sensorineural hearing impairment, sleep apnea, and a short stature. Renal anomalies were also observed although these resolved over time. She was found to have compound-heterozygous missense NCAPG2 mutations, c.1825A>G (p.Lys609Glu) and c.2078C>T (p.Thr693Met); three healthy siblings are either wild-type (WT) or heterozygous for the mutations (mut).
Family 2 - proband was a twin with multiple congenital anomalies at birth; these included microcephaly, facial dysmorphisms, digit abnormalities (postaxial absent toes and clinodactyly of the 5th finger), ocular phenotypes (Peters anomaly, bilateral glaucoma, and buphthalmos of the left eye), contractures, neonatal hypertonia, and a sacral dimple. A homozygous missense variant was found in the proband c.2548A>C [p.Thr850Pro]. Both parents are heterozygous for this variant.
Functional studies with skin fibroblasts from the proband in family 1, showed abnormal chromosome condensation, augmented anaphase chromatin-bridge formation, and micronuclei in daughter cells. In a ncapg2 zebrafish model, morphants displayed clinically relevant phenotypes, such as renal anomalies, microcephaly, and concomitant increases in apoptosis and altered mitotic progression. These could be rescued by wild-type but not mutant human NCAPG2 mRNA and were recapitulated in CRISPR-Cas9 F0 mutants.; to: Associated with Khan-Khan-Katsanis syndrome (#618460) in OMIM.

PMID: 30609410 - Khan et al. 2019 - 2 unrelated cases with homozygous or compound heterozygous variants in NCAPG2.
Family 1 - female with bilateral postaxial polydactyly on the feet, moderate intellectual disability, ocular anomalies, sensorineural hearing impairment, sleep apnea, and a short stature. Hydronephrosiss was also observed although this improved over time. She was found to have compound-heterozygous missense NCAPG2 mutations, c.1825A>G (p.Lys609Glu) and c.2078C>T (p.Thr693Met); three healthy siblings are either wild-type (WT) or heterozygous for the mutations (mut). Also of note was a heterozygous NPHP1 deletion, a common contributor to nephronophthisis.
Family 2 - proband was a twin with multiple congenital anomalies at birth; these included microcephaly, facial dysmorphisms, digit abnormalities (postaxial absent toes and clinodactyly of the 5th finger), ocular phenotypes (Peters anomaly, bilateral glaucoma, and buphthalmos of the left eye), contractures, neonatal hypertonia, and a sacral dimple. A homozygous missense variant was found in the proband c.2548A>C [p.Thr850Pro]. Both parents are heterozygous for this variant.
Functional studies with skin fibroblasts from the proband in family 1, showed abnormal chromosome condensation, augmented anaphase chromatin-bridge formation, and micronuclei in daughter cells. In a ncapg2 zebrafish model, morphants displayed clinically relevant phenotypes, such as renal anomalies, microcephaly, and concomitant increases in apoptosis and altered mitotic progression. These could be rescued by wild-type but not mutant human NCAPG2 mRNA and were recapitulated in CRISPR-Cas9 F0 mutants.
Limb disorders v1.35 NCAPG2 Eleanor Williams commented on gene: NCAPG2: Associated with Khan-Khan-Katsanis syndrome (#618460) in OMIM.

PMID: 30609410 - Khan et al. 2019 - 2 unrelated cases with homozygous or compound heterozygous variants in NCAPG2.
Family 1 - female with bilateral postaxial polydactyly on the feet, moderate intellectual disability, ocular anomalies, sensorineural hearing impairment, sleep apnea, and a short stature. Renal anomalies were also observed although these resolved over time. She was found to have compound-heterozygous missense NCAPG2 mutations, c.1825A>G (p.Lys609Glu) and c.2078C>T (p.Thr693Met); three healthy siblings are either wild-type (WT) or heterozygous for the mutations (mut).
Family 2 - proband was a twin with multiple congenital anomalies at birth; these included microcephaly, facial dysmorphisms, digit abnormalities (postaxial absent toes and clinodactyly of the 5th finger), ocular phenotypes (Peters anomaly, bilateral glaucoma, and buphthalmos of the left eye), contractures, neonatal hypertonia, and a sacral dimple. A homozygous missense variant was found in the proband c.2548A>C [p.Thr850Pro]. Both parents are heterozygous for this variant.
Functional studies with skin fibroblasts from the proband in family 1, showed abnormal chromosome condensation, augmented anaphase chromatin-bridge formation, and micronuclei in daughter cells. In a ncapg2 zebrafish model, morphants displayed clinically relevant phenotypes, such as renal anomalies, microcephaly, and concomitant increases in apoptosis and altered mitotic progression. These could be rescued by wild-type but not mutant human NCAPG2 mRNA and were recapitulated in CRISPR-Cas9 F0 mutants.
Limb disorders v1.35 NXN Eleanor Williams changed review comment from: Not associated with any phenotype in OMIM or Gene2Phenotype.

PMID: 29276006 - White et al 2018 - report 2 families with biallelic variants in NXN that co-segregate with Robinow syndrome. Family 1 - the proband has a several phenotypic features including the limb phenotypes of brachydactyly and mesomelic shortening, fifth finger brachydactyly and clinodactyly and broad thumbs and great toes. Family 2 - although her overall length was in the normal range, she had the appearance of short limbs and she had an unusual pattern of hand and foot development with brachydactyly and incurving of her fingers towards the middle finger. There was a wide sandal gap and the same clinodactyly pattern in her feet. Other craniofacial features were also present. A younger sibling was remarkably alike in terms of facial features and limb patterning.; to: Not associated with any phenotype in OMIM or Gene2Phenotype.

PMID: 29276006 - White et al 2018 - report 2 families with biallelic variants in NXN that co-segregate with Robinow syndrome. Family 1 - the proband has a several phenotypic features including the limb phenotypes of brachydactyly and mesomelic shortening, fifth finger brachydactyly and clinodactyly and broad thumbs and great toes. A homozygous stopgain variant in NXN c.625C>T [p.Arg209∗] was found to be inherited from consanguineous parents. Family 2 - although the overall length of the proband was in the normal range, she had the appearance of short limbs and she had an unusual pattern of hand and foot development with brachydactyly and incurving of her fingers towards the middle finger. There was a wide sandal gap and the same clinodactyly pattern in her feet. Other craniofacial features were also present. A younger sibling was remarkably alike in terms of facial features and limb patterning. The siblings shared compound heterozygous biallelic variants in NXN: a maternally inherited in-frame 3-bp deletion (c.1234_1236del [p.Glu412del]) and a paternally inherited intragenic 84-kb deletion that encompasses the entire first exon chr17:g.805043::GAGG…..AATG::889090).
Limb disorders v1.35 NXN Eleanor Williams Added comment: Comment on mode of inheritance: 2 cases to date are biallelic
Limb disorders v1.35 NXN Eleanor Williams Mode of inheritance for gene: NXN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v1.34 NXN Eleanor Williams Phenotypes for gene: NXN were changed from to Robinow syndrome
Limb disorders v1.33 NXN Eleanor Williams commented on gene: NXN: Not associated with any phenotype in OMIM or Gene2Phenotype.

PMID: 29276006 - White et al 2018 - report 2 families with biallelic variants in NXN that co-segregate with Robinow syndrome. Family 1 - the proband has a several phenotypic features including the limb phenotypes of brachydactyly and mesomelic shortening, fifth finger brachydactyly and clinodactyly and broad thumbs and great toes. Family 2 - although her overall length was in the normal range, she had the appearance of short limbs and she had an unusual pattern of hand and foot development with brachydactyly and incurving of her fingers towards the middle finger. There was a wide sandal gap and the same clinodactyly pattern in her feet. Other craniofacial features were also present. A younger sibling was remarkably alike in terms of facial features and limb patterning.
Limb disorders v1.33 NXN Eleanor Williams Publications for gene: NXN were set to
Limb disorders v1.32 FZD2 Eleanor Williams Phenotypes for gene: FZD2 were changed from to Omodysplasia 2, 164745; Robinow syndrome
Limb disorders v1.31 FZD2 Eleanor Williams Publications for gene: FZD2 were set to 29276006
Limb disorders v1.30 FZD2 Eleanor Williams commented on gene: FZD2: Associated with Omodysplasia 2 (#164745) in OMIM.

Omodysplasia 2:

PMID: 25759469 - Saal et al. 2015 - 1 case - a mother and daughter with omodysplasia were found to have a FZD2 mutation (c.1644G>A, p.Trp548*). The variant was found to have occurred de novo in the mother. The altered protein is still produced in vitro, but is shown to have reduced ability to interact with its downstream target DISHEVELLED. The mother had multiple anomalies, including bilateral cleft lip and cleft palate, short upper extremities, dysmorphic facial features and hypoplastic labia and clitoris. Skeletal X rays of the daughter showed hypoplasia of T11 vertebral body and bilateral dislocation of the radius with short humeri. At 6 years musculoskeletal examination showed primarily rhizomelic shortening of the upper extremities and a mild shortening of the forearms with limited forearm supination/pronation. There was mild fifth finger clinodactyly with no brachydactyly.

Robinow syndrome:

PMID: 29276006 - White et al 2018 - 4 families with at least one individual clinical diagnosed with Robinow or Robinow-like phenotypes and with variants in FZD2 were identified . All showed limb phenotypes including mesomelic limb shortening (3 families, mild in one case), brachdactyly (3 families), proximaly implanted thumbs (1 family), Medelung deformity (1 family).
Limb disorders v1.30 FZD2 Eleanor Williams Publications for gene: FZD2 were set to
Limb disorders v1.29 ASXL1 Eleanor Williams Publications for gene: ASXL1 were set to
Limb disorders v1.28 ASXL1 Eleanor Williams Phenotypes for gene: ASXL1 were changed from to Bohring-Opitz syndrome, 605039
Limb disorders v1.27 ASXL1 Eleanor Williams commented on gene: ASXL1: Associated with Bohring-Opitz syndrome 605039 in OMIM and Gene2Phenotype (confirmed).

PMID: 21706002 - Hoischen et al. 2011 - 7 cases - sequenced 13 unrelated patients with Bohring-Opitz syndrome and found de novo heterozygous mutations in 7 of them. All 7 showed a typical BOS posture with flexed elbows and wrists and ulnar deviation of wrists and metacarpophalangeal joints. Syndactyly was observed in 3 out of the 7. Fixed contractures were observed in 6/7.

PMID: 22419483 - Magini et al. 2012 - In 2 unrelated patients with classic features of Bohring-Opitz syndrome, identified 2 different de novo heterozygous truncating mutations in the ASXL1 gene not previously reported. Patient 1 - axial hypotonia, limitation of elbow extension, right talipes valgus, and typical facial appearance: prominent forehead, hemangioma over the forehead and glabella, exophthalmos, ptosis, hypertelorism, low‐set, and posteriorly angulated ears, long philtrum, and everted lower lip. Patient 2 had multiple phenotypic features that include flexion deformities of upper limbs joints, at elbow and wrist level with ulnar deviation of both hands, overlapping digits, abduced thumb, clenched fists, deep single palmar crease, typical BOS posture and hypertonia, with contractures at hips, knees, and ankles. Talo‐valgus deformity of feet was present
Limb disorders v1.27 PAX3 Eleanor Williams Publications for gene: PAX3 were set to
Limb disorders v1.26 PAX3 Eleanor Williams Phenotypes for gene: PAX3 were changed from to Waardenburg syndrome, type 3, 148820
Limb disorders v1.25 PAX3 Eleanor Williams Mode of inheritance for gene: PAX3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Limb disorders v1.24 PAX3 Eleanor Williams changed review comment from: Associated with Waardenburg syndrome, type 3 (148820) and Craniofacial-deafness-hand syndrome (122880) in OMIM. It is also associated with Waardenburg syndrome type 1 (193500) which presents with a milder phenotype.

Waardenburg syndrome, type 3:

PMID: 7726174- Zlotogora et al. 1995 - 1 family - a large kindred with Waardenburg syndrome type 1 and a heterozygous mutation S84F in PAX3 gene. 1 child, born of consanguineous parents, had a severe phenotype consistent with WS type 3. This child was homozygous for the S84F mutation. The child presented with dystopia canthorum, partial albinism, and very severe upper limb defects.

PMID: 8447316 - Hoth et al. 1993 - 1 family - report the identification of a heterozygous variant leading to a N47H substitution in PAX3 (exon 2) in affected members of a family with Waardenburg syndrome type 3. In addition to hearing loss and dystopia canthorum, affected members of this family have both third-fifth-finger bilateral camptodactyly with proximal insertion of the thumbs and other limb abnormalities. The family were previously reported by Milunsky et al. (1992), Goodman et al. (1982) and Sheffer and Zlotogora (1992).

PMID: 11683776 - Tekin et al. 2001 - describe a mother and son with typical clinical findings of WS type 3 segregating with a heterozygous 13-bp deletion in the paired domain in exon 3 of the PAX3 gene. However, the limb phenotype is restricted to slight flexion contractures of the fingers, especially involving the ulnar ray in the mother, and bilateral flexion contractures of the fingers especially of the lateral three digits in the son.

PMID: 12949970 - Wollnik et al. 2003 - 1 family - a consanguineous Turkish family with a daughter in which a homozygous variant in the PAX3 gene resulted in a Y90H substitution. Both parents were heterozygous for the variant. . The daughter was determined to have type 3 Waardenburg syndrome. The limb phenotype includes flexion deformities of wrists and fingers with ulnar deviation, decreased palmar creases, and minimal webs between fingers were noted.

PMID: 30173992 - Saberi et al 2018 - 1 family - Iranian family with 10 affected members with WS type 1 or type 3. A donor splice site variant (c.586 + 2 T > C) was found in intron 4 of PAX3 that was predicted to be deleterious and co-segregated in the pedigree. It was not found in asymptomatic members. Of the 6 family members for which clinical features are available, 3 showed camptodactyly along with other features such as Hypertelorism, Dystopia Canthorum, and Broad/high nasal root. Hearing loss was not observed.; to: Associated with Waardenburg syndrome, type 3 (148820) and Craniofacial-deafness-hand syndrome (122880) in OMIM. It is also associated with Waardenburg syndrome type 1 (193500) which presents with a milder phenotype.

Waardenburg syndrome, type 3:

Homozygous cases:

PMID: - not available - Bottani et al., 1999 - 1 case originally reported in Klein et al 1983 (PMID: 6340503) of compound heterozygous mutations in PAX3 involving a recurrent missense mutation in the homeodomain and a new one in the paired domain in an individual with WS3. (Full publications not accessed).

PMID: 12949970 - Wollnik et al. 2003 - 1 family - a consanguineous Turkish family with a daughter in which a homozygous variant in the PAX3 gene resulted in a Y90H substitution. Both parents were heterozygous for the variant. The daughter was determined to have type 3 Waardenburg syndrome. The limb phenotype includes flexion deformities of wrists and fingers with ulnar deviation, decreased palmar creases, and minimal webs between fingers were noted.

PMID: 7726174- Zlotogora et al. 1995 - 1 case - a large kindred with Waardenburg syndrome type 1 and a heterozygous mutation S84F in PAX3 gene. 1 child, born of consanguineous parents, had a severe phenotype consistent with WS type 3. This child was homozygous for the S84F mutation. The child presented with dystopia canthorum, partial albinism, and very severe upper limb defects. Severe changes were present in the
upper limbs, with rigidity of the larger joints -including shoulders, elbows, and wrists-as well as of the smaller
joints of the fingers. Muscle wasting was severe in the pectoral region, the shoulders, and upper limbs. Axillary
webs were present on both sides. There was a slight degree of contracture of the knees, and there was calcaneovalgus deformation of the feet.

PMID: 26443304 - Mousty et al 2015 - 1 case - parents were first‐cousin relatives from a gypsy community in the south of France which both presented with a typical WS1 profile. Ultrasound examination of the fetus revealed cystic hygroma, holoprosencephaly, a lack of active movements, extremity abnormalities (short long bones associated with bilateral club hand and club foot), and significant spinal curvature. Both parents were found to have the same heterozygous mutation in exon 6 of PAX3, namely c.807C>G (p.Asn269Lys). Sequencing of fetal DNA found the mutation in the homozygous state. Functional studies showed an almost total loss of function of PAX3 co‐activation with SOX10 when it came to the mutant.

Heterozygous cases:

PMID: 8447316 - Hoth et al. 1993 - 1 family - report the identification of a heterozygous variant leading to a N47H substitution in PAX3 (exon 2) in affected members of a family with Waardenburg syndrome type 3. In addition to hearing loss and dystopia canthorum, affected members of this family have both third-fifth-finger bilateral camptodactyly with proximal insertion of the thumbs and other limb abnormalities. The family were previously reported by Milunsky et al. (1992), Goodman et al. (1982) and Sheffer and Zlotogora (1992).

PMID: 11683776 - Tekin et al. 2001 - describe a mother and son with typical clinical findings of WS type 3 segregating with a heterozygous 13-bp deletion in the paired domain in exon 3 of the PAX3 gene. However, the limb phenotype is restricted to slight flexion contractures of the fingers, especially involving the ulnar ray in the mother, and bilateral flexion contractures of the fingers especially of the lateral three digits in the son.

PMID: 30173992 - Saberi et al 2018 - 1 family - Iranian family with 10 affected members with WS type 1 or type 3. A heterozygous donor splice site variant (c.586 + 2 T > C) was found in intron 4 of PAX3 that was predicted to be deleterious and co-segregated in the pedigree. It was not found in asymptomatic members. Of the 6 family members for which clinical features are available, 3 showed camptodactyly along with other features such as Hypertelorism, Dystopia Canthorum, and Broad/high nasal root. Hearing loss was not observed.
Limb disorders v1.24 PAX3 Eleanor Williams commented on gene: PAX3: Associated with Waardenburg syndrome, type 3 (148820) and Craniofacial-deafness-hand syndrome (122880) in OMIM. It is also associated with Waardenburg syndrome type 1 (193500) which presents with a milder phenotype.

Waardenburg syndrome, type 3:

PMID: 7726174- Zlotogora et al. 1995 - 1 family - a large kindred with Waardenburg syndrome type 1 and a heterozygous mutation S84F in PAX3 gene. 1 child, born of consanguineous parents, had a severe phenotype consistent with WS type 3. This child was homozygous for the S84F mutation. The child presented with dystopia canthorum, partial albinism, and very severe upper limb defects.

PMID: 8447316 - Hoth et al. 1993 - 1 family - report the identification of a heterozygous variant leading to a N47H substitution in PAX3 (exon 2) in affected members of a family with Waardenburg syndrome type 3. In addition to hearing loss and dystopia canthorum, affected members of this family have both third-fifth-finger bilateral camptodactyly with proximal insertion of the thumbs and other limb abnormalities. The family were previously reported by Milunsky et al. (1992), Goodman et al. (1982) and Sheffer and Zlotogora (1992).

PMID: 11683776 - Tekin et al. 2001 - describe a mother and son with typical clinical findings of WS type 3 segregating with a heterozygous 13-bp deletion in the paired domain in exon 3 of the PAX3 gene. However, the limb phenotype is restricted to slight flexion contractures of the fingers, especially involving the ulnar ray in the mother, and bilateral flexion contractures of the fingers especially of the lateral three digits in the son.

PMID: 12949970 - Wollnik et al. 2003 - 1 family - a consanguineous Turkish family with a daughter in which a homozygous variant in the PAX3 gene resulted in a Y90H substitution. Both parents were heterozygous for the variant. . The daughter was determined to have type 3 Waardenburg syndrome. The limb phenotype includes flexion deformities of wrists and fingers with ulnar deviation, decreased palmar creases, and minimal webs between fingers were noted.

PMID: 30173992 - Saberi et al 2018 - 1 family - Iranian family with 10 affected members with WS type 1 or type 3. A donor splice site variant (c.586 + 2 T > C) was found in intron 4 of PAX3 that was predicted to be deleterious and co-segregated in the pedigree. It was not found in asymptomatic members. Of the 6 family members for which clinical features are available, 3 showed camptodactyly along with other features such as Hypertelorism, Dystopia Canthorum, and Broad/high nasal root. Hearing loss was not observed.
Limb disorders v1.24 EPHA4 Andrew Wilkie reviewed gene: EPHA4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 SOX9 Andrew Wilkie reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 SMAD6 Andrew Wilkie reviewed gene: SMAD6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 STKLD1 Andrew Wilkie reviewed gene: STKLD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 POLR1A Andrew Wilkie reviewed gene: POLR1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 GZF1 Andrew Wilkie reviewed gene: GZF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 SUFU Andrew Wilkie reviewed gene: SUFU: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 TRAF7 Andrew Wilkie reviewed gene: TRAF7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 NCAPG2 Andrew Wilkie reviewed gene: NCAPG2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 NXN Andrew Wilkie reviewed gene: NXN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 FZD2 Andrew Wilkie reviewed gene: FZD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 ASXL1 Andrew Wilkie reviewed gene: ASXL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 PAX3 Andrew Wilkie reviewed gene: PAX3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 EIF4A3 Andrew Wilkie reviewed gene: EIF4A3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 CYP26B1 Andrew Wilkie reviewed gene: CYP26B1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 ZSWIM6 Andrew Wilkie reviewed gene: ZSWIM6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.24 EFNB1 Andrew Wilkie reviewed gene: EFNB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v1.23 EPHA4 Eleanor Williams gene: EPHA4 was added
gene: EPHA4 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: EPHA4 was set to Unknown
Review for gene: EPHA4 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.22 SMAD6 Eleanor Williams gene: SMAD6 was added
gene: SMAD6 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: SMAD6 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.21 STKLD1 Eleanor Williams gene: STKLD1 was added
gene: STKLD1 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: STKLD1 was set to Unknown
Review for gene: STKLD1 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.20 POLR1A Eleanor Williams gene: POLR1A was added
gene: POLR1A was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: POLR1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: POLR1A was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.19 GZF1 Eleanor Williams gene: GZF1 was added
gene: GZF1 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: GZF1 was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.18 SUFU Eleanor Williams gene: SUFU was added
gene: SUFU was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: SUFU was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: SUFU was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.17 TRAF7 Eleanor Williams gene: TRAF7 was added
gene: TRAF7 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: TRAF7 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.16 NCAPG2 Eleanor Williams gene: NCAPG2 was added
gene: NCAPG2 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: NCAPG2 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: NCAPG2 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.15 NXN Eleanor Williams gene: NXN was added
gene: NXN was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: NXN was set to Unknown
Review for gene: NXN was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.14 FZD2 Eleanor Williams gene: FZD2 was added
gene: FZD2 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: FZD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: FZD2 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.13 ASXL1 Eleanor Williams gene: ASXL1 was added
gene: ASXL1 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: ASXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: ASXL1 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.12 PAX3 Eleanor Williams gene: PAX3 was added
gene: PAX3 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: PAX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: PAX3 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.11 EIF4A3 Eleanor Williams gene: EIF4A3 was added
gene: EIF4A3 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: EIF4A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF4A3 were set to 9284755; 9449664
Phenotypes for gene: EIF4A3 were set to Robin sequence with cleft mandible and limb anomalies, 268305
Review for gene: EIF4A3 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.10 CYP26B1 Eleanor Williams commented on gene: CYP26B1: Associated with Craniosynostosis with radiohumeral fusions and other skeletal and craniofacial anomalies (614416) in OMIM.

PMID: 22019272 - Laue et al 2011 - 2 cases, 1 with a relevant limb phenotype. Family 1 - three siblings born to first-cousin parents who exhibited combinations of severe craniofacial malformations, occipital encephalocele, radiohumeral fusions, oligodactyly, advanced osseous maturation, and calvarial mineralization defects. First proband presented as a fetal death, and subsequent second and third sibs were identified as affected by ultrasonography in two separate pregnancies. Homozygosity for p.Arg363Leu in CYP26B1 was found in all 3 sibs. The parents were heterozygous. Family 2 - individual with a likely diagnosis of Antley-Bixler syndrome born to consanguineous parents. Homozygosity for p.Ser146Pro was found. The phenotype of this female included coronal and lambdoid craniosynostosis, a large sagittal skull defect, limited elbow extension, and arachnodactyly.

PMID: 27410456 - Morton et al 2016 - 1 case. A woman homozygous for c.1303G>A; p.(Gly435Ser) in CYP26B1, which was associated with multisutural synostosis, radiohumeral synostosis, normal bone mineral density, and apparent intellectual disability. Reported limb phenotypes are camptodactyly of the fingers, long and narrow feet, short third and fourth metatarsals, and small third to fifth toenails.
Limb disorders v1.10 CYP26B1 Eleanor Williams gene: CYP26B1 was added
gene: CYP26B1 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: CYP26B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP26B1 were set to 22019272; 27410456
Phenotypes for gene: CYP26B1 were set to Craniosynostosis with radiohumeral fusions and other skeletal and craniofacial anomalies, 614416
Review for gene: CYP26B1 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.9 EFNB1 Eleanor Williams commented on gene: EFNB1: Associated with Craniofrontonasal dysplasia (304110) in OMIM and CRANIOFRONTONASAL SYNDROME in Gene2Phenotype (confirmed). In OMIM Asymmetric lower limb shortness, Joint laxity, Syndactyly, Brachydactyly, Fifth finger clinodactyly and Broad halluces are listed as limb features of the condition and a similar list is given in Gene2Phenotype.

CFNS shows a very unusual pattern of X-linked inheritance, in which most affected patients are females and obligate male carriers show no or only mild manifestation, such as hypertelorism .

PMID: 15166289 - Twigg et al 2014 - identified significant mutations in EFNB1 in all 20 unrelated Craniofrontonasal syndrome females studied, including nine different de novo mutations. Of the 20, 2 had duplex thumb/hallux and 1 showed lower-limb asymmetry in addition to other features such as coronal craniosynostosis and cleft lip and/or palate.

PMID: 23335590 - Twigg et al 2013 - Six severely affected sporadic males with a diagnosis of CFNS. They identified mosaic mutations of EFNB1 in all cases, comprising three missense changes, two gene deletions and a novel point mutation within the 5′ untranslated region (UTR). 4/6 patients had brachydactyly and/or syndactyly. Clinodactyly was also seen in 3 patients.

PMID: 15124102 - Weiland et al 2004 - 3 families with variants (deletion of exons 2–5 and two missense variants) in EFNB1 and CFNS. In Family 2 brachydactyly was an observed phenotype. In Family 3 one female showed complete syndactyly of the third and fourth finger on the left side.
Limb disorders v1.9 EFNB1 Eleanor Williams gene: EFNB1 was added
gene: EFNB1 was added to Limb disorders. Sources: Expert list
Mode of inheritance for gene: EFNB1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: EFNB1 were set to 15166289; 23335590; 15124102
Phenotypes for gene: EFNB1 were set to Craniofrontonasal syndrome, 304110
Mode of pathogenicity for gene: EFNB1 was set to Other
Review for gene: EFNB1 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Limb disorders v1.8 RBPJ Eleanor Williams Publications for gene: RBPJ were set to 22883147; 28160419
Limb disorders v1.7 RBPJ Eleanor Williams commented on gene: RBPJ
Limb disorders v1.7 SOX9 Louise Daugherty Tag duplication was removed from gene: SOX9.
Tag gene-duplication tag was added to gene: SOX9.
Limb disorders v1.5 C5orf42 Louise Daugherty Tag new-gene-name tag was added to gene: C5orf42.
Limb disorders v1.5 C5orf42 Louise Daugherty commented on gene: C5orf42
Limb disorders v1.4 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel
Limb disorders v1.0 Eleanor Williams promoted panel to version 1.0
Limb disorders v0.361 FANCB Eleanor Williams commented on gene: FANCB
Limb disorders v0.361 LZTFL1 Eleanor Williams Classified gene: LZTFL1 as No list
Limb disorders v0.361 LZTFL1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is on the Rare multisystem ciliopathy disorders panel (v1.79) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded. Currently red on cilliopathy panel but this will be reviewed.
Limb disorders v0.361 LZTFL1 Eleanor Williams Gene: lztfl1 has been removed from the panel.
Limb disorders v0.359 CCND2 Eleanor Williams Added comment: Comment on mode of pathogenicity: PMID: 24705253 functional analysis suggests gain of function
Limb disorders v0.359 CCND2 Eleanor Williams Mode of pathogenicity for gene: CCND2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Limb disorders v0.358 TBX4 Eleanor Williams Phenotypes for gene: TBX4 were changed from Ischiocoxopodopatellar syndrome to Ischiocoxopodopatellar syndrome 147891
Limb disorders v0.357 RBM8A Eleanor Williams Phenotypes for gene: RBM8A were changed from Thrombocytopenia-absent radius syndrome, 274000; Thrombocytopenia-absent radius syndrome 274000 to Thrombocytopenia-absent radius syndrome, 274000
Limb disorders v0.356 RAB23 Eleanor Williams Phenotypes for gene: RAB23 were changed from Carpenter syndrome 201000; Polydactyly to Carpenter syndrome 201000; Polydactyly; ACROCEPHALOPOLYSYNDACTYLY TYPE 2
Limb disorders v0.355 PTHLH Eleanor Williams Phenotypes for gene: PTHLH were changed from Brachydactyly, type E2 to Brachydactyly, type E2 613382
Limb disorders v0.354 LMX1B Eleanor Williams Phenotypes for gene: LMX1B were changed from Nail-patella syndrome to Nail-patella syndrome 161200
Limb disorders v0.353 HDAC4 Eleanor Williams commented on gene: HDAC4
Limb disorders v0.353 BHLHA9 Eleanor Williams Publications for gene: BHLHA9 were set to
Limb disorders v0.352 BHLHA9 Eleanor Williams Added comment: Comment on mode of inheritance: Changing MOI back to biallelic only, as the duplication of this gene in SPLIT HAND AND FOOT MALFORMATION seems to be more of a susceptibility factor.
Limb disorders v0.352 BHLHA9 Eleanor Williams Mode of inheritance for gene: BHLHA9 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.351 ABL1 Eleanor Williams Classified gene: ABL1 as Amber List (moderate evidence)
Limb disorders v0.351 ABL1 Eleanor Williams Added comment: Comment on list classification: Downgraded to Amber on advice from Genomics England clinical team.
Limb disorders v0.351 ABL1 Eleanor Williams Gene: abl1 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.350 ORC1 Eleanor Williams Marked gene: ORC1 as ready
Limb disorders v0.350 ORC1 Eleanor Williams Added comment: Comment when marking as ready: checked by clinical team
Limb disorders v0.350 ORC1 Eleanor Williams Gene: orc1 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.350 ORC1 Eleanor Williams commented on gene: ORC1: Genomics England clinical team agree with Amber rating since Meier-Gorlin is a phenotype associated with generalised short stature and microcephaly rather than more focal limb phenotype. It is more likely to be picked up via other panels such as Primary Microcephaly - Microcephalic Dwarfism Spectrum and Unexplained skeletal dysplasia panels.
Limb disorders v0.350 DVL1 Eleanor Williams Publications for gene: DVL1 were set to 25817016
Limb disorders v0.349 DVL1 Eleanor Williams Publications for gene: DVL1 were set to
Limb disorders v0.348 DVL1 Eleanor Williams Added comment: Comment on mode of pathogenicity: PMID:25817016 suggests known variants causing Robinow syndrome are gain of function
Limb disorders v0.348 DVL1 Eleanor Williams Mode of pathogenicity for gene: DVL1 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Limb disorders v0.347 BHLHA9 Eleanor Williams Mode of inheritance for gene: BHLHA9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb disorders v0.346 WNT5A Eleanor Williams Added comment: Comment on mode of inheritance: Changed to imprinted status unknown as reviewer had selected this.
Limb disorders v0.346 WNT5A Eleanor Williams Mode of inheritance for gene: WNT5A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.345 TRPS1 Eleanor Williams Added comment: Comment on mode of inheritance: Changed to imprinted status unknown as reviewer had selected this.
Limb disorders v0.345 TRPS1 Eleanor Williams Mode of inheritance for gene: TRPS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.344 TP63 Eleanor Williams Added comment: Comment on mode of inheritance: Changed to imprinted status unknown as reviewer had selected this.
Limb disorders v0.344 TP63 Eleanor Williams Mode of inheritance for gene: TP63 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.343 ABL1 Rebecca Foulger Added comment: Comment on mode of pathogenicity: Both variants reported so far in PMID:28288113 are missense.
Limb disorders v0.343 ABL1 Rebecca Foulger Mode of pathogenicity for gene: ABL1 was changed from None to Other
Limb disorders v0.342 ABL1 Rebecca Foulger Classified gene: ABL1 as Green List (high evidence)
Limb disorders v0.342 ABL1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green: ABL1 was originally added to the TAAD panel by the external reviewer Chris Buxton. The phenotypes reported in PMID:28288113 are appropriate for inclusion on the limb panel (including clinodactyly, arachnodactyly, camptodactylyly) and seen in sufficient cases (>3 families, 2 missense variants) for a diagnostic rating.
Limb disorders v0.342 ABL1 Rebecca Foulger Gene: abl1 has been classified as Green List (High Evidence).
Limb disorders v0.341 ABL1 Rebecca Foulger commented on gene: ABL1: Digit anomalies were seen in all four families from PMID:28288113: Subject 1 (family 1) had a hindfoot deformity. Subject 2 (family 1) had long fingers and toes. Subject 3 (family 2), had 5th finger clinodactyly bilaterally. Subject 4 (family 3) had clinodactyly of the 5th fingers. Subject 5 (family 3) had arachnodactyly (Spider hands), Subject 6 (family 4) had bilateral camptodactylyly of little fingers and bilateral 2-3 toe syndactyly.
Limb disorders v0.341 ABL1 Rebecca Foulger gene: ABL1 was added
gene: ABL1 was added to Limb disorders. Sources: Literature
Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ABL1 were set to 28288113
Phenotypes for gene: ABL1 were set to congential heart disease, skeletal abnormalities and failure to thrive; clinodactyly; syndactyly; arachnodactyly
Added comment: Wang et al.,2017 (PMID:28288113) report ABL1 germline variants cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. The variant c.734A>G (p.Tyr245Cys) was found to occur de novo in 3 individuals (families 1-2) and in family 3, the variant was seen in the affected father and daughter. Additionally, a de novo c.1066G>A (p.Ala356Thr) variant was identified in a sixth individual (family 4). Functional assays show that both missense variants cause increased phosphorylation, suggesting increased ABL1 kinase activity.
Sources: Literature
Limb disorders v0.340 TBX4 Eleanor Williams Added comment: Comment on mode of inheritance: Changing to imprinted status unknown as per the reviewer selection.
Limb disorders v0.340 TBX4 Eleanor Williams Mode of inheritance for gene: TBX4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.339 WDR60 Eleanor Williams Publications for gene: WDR60 were set to
Limb disorders v0.338 LBR Eleanor Williams Publications for gene: LBR were set to 18382993; 12618959; 21327084; 12118250
Limb disorders v0.337 LBR Eleanor Williams commented on gene: LBR
Limb disorders v0.337 WDR60 Eleanor Williams commented on gene: WDR60
Limb disorders v0.337 ZIC3 Eleanor Williams commented on gene: ZIC3
Limb disorders v0.337 ZSWIM6 Eleanor Williams Classified gene: ZSWIM6 as No list
Limb disorders v0.337 ZSWIM6 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.337 ZSWIM6 Eleanor Williams Gene: zswim6 has been removed from the panel.
Limb disorders v0.336 WDR35 Eleanor Williams Classified gene: WDR35 as No list
Limb disorders v0.336 WDR35 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.336 WDR35 Eleanor Williams Gene: wdr35 has been removed from the panel.
Limb disorders v0.335 WDR34 Eleanor Williams Classified gene: WDR34 as No list
Limb disorders v0.335 WDR34 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.335 WDR34 Eleanor Williams Gene: wdr34 has been removed from the panel.
Limb disorders v0.334 WDR19 Eleanor Williams Classified gene: WDR19 as No list
Limb disorders v0.334 WDR19 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.334 WDR19 Eleanor Williams Gene: wdr19 has been removed from the panel.
Limb disorders v0.333 WDPCP Eleanor Williams Classified gene: WDPCP as No list
Limb disorders v0.333 WDPCP Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.333 WDPCP Eleanor Williams Gene: wdpcp has been removed from the panel.
Limb disorders v0.332 TTC8 Eleanor Williams Marked gene: TTC8 as ready
Limb disorders v0.332 TTC8 Eleanor Williams Gene: ttc8 has been removed from the panel.
Limb disorders v0.332 TTC8 Eleanor Williams Classified gene: TTC8 as No list
Limb disorders v0.332 TTC8 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.332 TTC8 Eleanor Williams Gene: ttc8 has been removed from the panel.
Limb disorders v0.331 TTC21B Eleanor Williams Marked gene: TTC21B as ready
Limb disorders v0.331 TTC21B Eleanor Williams Gene: ttc21b has been removed from the panel.
Limb disorders v0.331 TTC21B Eleanor Williams Classified gene: TTC21B as No list
Limb disorders v0.331 TTC21B Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.331 TTC21B Eleanor Williams Gene: ttc21b has been removed from the panel.
Limb disorders v0.330 TRAF3IP1 Eleanor Williams Marked gene: TRAF3IP1 as ready
Limb disorders v0.330 TRAF3IP1 Eleanor Williams Gene: traf3ip1 has been removed from the panel.
Limb disorders v0.330 TRAF3IP1 Eleanor Williams Classified gene: TRAF3IP1 as No list
Limb disorders v0.330 TRAF3IP1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.330 TRAF3IP1 Eleanor Williams Gene: traf3ip1 has been removed from the panel.
Limb disorders v0.329 TMEM67 Eleanor Williams Marked gene: TMEM67 as ready
Limb disorders v0.329 TMEM67 Eleanor Williams Gene: tmem67 has been removed from the panel.
Limb disorders v0.329 TMEM67 Eleanor Williams Classified gene: TMEM67 as No list
Limb disorders v0.329 TMEM67 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.329 TMEM67 Eleanor Williams Gene: tmem67 has been removed from the panel.
Limb disorders v0.328 TMEM237 Eleanor Williams Marked gene: TMEM237 as ready
Limb disorders v0.328 TMEM237 Eleanor Williams Gene: tmem237 has been removed from the panel.
Limb disorders v0.328 TMEM237 Eleanor Williams Classified gene: TMEM237 as No list
Limb disorders v0.328 TMEM237 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.328 TMEM237 Eleanor Williams Gene: tmem237 has been removed from the panel.
Limb disorders v0.327 TMEM231 Eleanor Williams Marked gene: TMEM231 as ready
Limb disorders v0.327 TMEM231 Eleanor Williams Gene: tmem231 has been removed from the panel.
Limb disorders v0.327 TMEM231 Eleanor Williams Classified gene: TMEM231 as No list
Limb disorders v0.327 TMEM231 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.327 TMEM231 Eleanor Williams Gene: tmem231 has been removed from the panel.
Limb disorders v0.326 TMEM216 Eleanor Williams Marked gene: TMEM216 as ready
Limb disorders v0.326 TMEM216 Eleanor Williams Gene: tmem216 has been removed from the panel.
Limb disorders v0.326 TMEM216 Eleanor Williams Classified gene: TMEM216 as No list
Limb disorders v0.326 TMEM216 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.326 TMEM216 Eleanor Williams Gene: tmem216 has been removed from the panel.
Limb disorders v0.325 TMEM138 Eleanor Williams Marked gene: TMEM138 as ready
Limb disorders v0.325 TMEM138 Eleanor Williams Gene: tmem138 has been removed from the panel.
Limb disorders v0.325 TMEM138 Eleanor Williams Classified gene: TMEM138 as No list
Limb disorders v0.325 TMEM138 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.325 TMEM138 Eleanor Williams Gene: tmem138 has been removed from the panel.
Limb disorders v0.324 TCTN3 Eleanor Williams Classified gene: TCTN3 as No list
Limb disorders v0.324 TCTN3 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.324 TCTN3 Eleanor Williams Gene: tctn3 has been removed from the panel.
Limb disorders v0.323 TCTN2 Eleanor Williams Classified gene: TCTN2 as No list
Limb disorders v0.323 TCTN2 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.323 TCTN2 Eleanor Williams Gene: tctn2 has been removed from the panel.
Limb disorders v0.322 TCTEX1D2 Eleanor Williams Classified gene: TCTEX1D2 as No list
Limb disorders v0.322 TCTEX1D2 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.322 TCTEX1D2 Eleanor Williams Gene: tctex1d2 has been removed from the panel.
Limb disorders v0.321 SDCCAG8 Eleanor Williams Marked gene: SDCCAG8 as ready
Limb disorders v0.321 SDCCAG8 Eleanor Williams Gene: sdccag8 has been removed from the panel.
Limb disorders v0.321 SDCCAG8 Eleanor Williams Classified gene: SDCCAG8 as No list
Limb disorders v0.321 SDCCAG8 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.321 SDCCAG8 Eleanor Williams Gene: sdccag8 has been removed from the panel.
Limb disorders v0.320 RPGRIP1L Eleanor Williams Marked gene: RPGRIP1L as ready
Limb disorders v0.320 RPGRIP1L Eleanor Williams Gene: rpgrip1l has been removed from the panel.
Limb disorders v0.320 RPGRIP1L Eleanor Williams Classified gene: RPGRIP1L as No list
Limb disorders v0.320 RPGRIP1L Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.320 RPGRIP1L Eleanor Williams Gene: rpgrip1l has been removed from the panel.
Limb disorders v0.319 OFD1 Eleanor Williams Marked gene: OFD1 as ready
Limb disorders v0.319 OFD1 Eleanor Williams Gene: ofd1 has been removed from the panel.
Limb disorders v0.319 OFD1 Eleanor Williams Classified gene: OFD1 as No list
Limb disorders v0.319 OFD1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.319 OFD1 Eleanor Williams Gene: ofd1 has been removed from the panel.
Limb disorders v0.318 NPHP3 Eleanor Williams Marked gene: NPHP3 as ready
Limb disorders v0.318 NPHP3 Eleanor Williams Gene: nphp3 has been removed from the panel.
Limb disorders v0.318 NPHP3 Eleanor Williams Classified gene: NPHP3 as No list
Limb disorders v0.318 NPHP3 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.318 NPHP3 Eleanor Williams Gene: nphp3 has been removed from the panel.
Limb disorders v0.317 NEK1 Eleanor Williams Classified gene: NEK1 as No list
Limb disorders v0.317 NEK1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.317 NEK1 Eleanor Williams Gene: nek1 has been removed from the panel.
Limb disorders v0.316 MKS1 Eleanor Williams Marked gene: MKS1 as ready
Limb disorders v0.316 MKS1 Eleanor Williams Gene: mks1 has been removed from the panel.
Limb disorders v0.316 MKS1 Eleanor Williams Classified gene: MKS1 as No list
Limb disorders v0.316 MKS1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.316 MKS1 Eleanor Williams Gene: mks1 has been removed from the panel.
Limb disorders v0.315 MKKS Eleanor Williams Marked gene: MKKS as ready
Limb disorders v0.315 MKKS Eleanor Williams Gene: mkks has been removed from the panel.
Limb disorders v0.315 MKKS Eleanor Williams Classified gene: MKKS as No list
Limb disorders v0.315 MKKS Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.315 MKKS Eleanor Williams Gene: mkks has been removed from the panel.
Limb disorders v0.314 KIF7 Eleanor Williams Marked gene: KIF7 as ready
Limb disorders v0.314 KIF7 Eleanor Williams Gene: kif7 has been removed from the panel.
Limb disorders v0.314 KIF7 Eleanor Williams Classified gene: KIF7 as No list
Limb disorders v0.314 KIF7 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.314 KIF7 Eleanor Williams Gene: kif7 has been removed from the panel.
Limb disorders v0.313 KIAA0586 Eleanor Williams Classified gene: KIAA0586 as No list
Limb disorders v0.313 KIAA0586 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.313 KIAA0586 Eleanor Williams Gene: kiaa0586 has been removed from the panel.
Limb disorders v0.312 INPP5E Eleanor Williams Marked gene: INPP5E as ready
Limb disorders v0.312 INPP5E Eleanor Williams Gene: inpp5e has been removed from the panel.
Limb disorders v0.312 INPP5E Eleanor Williams Classified gene: INPP5E as No list
Limb disorders v0.312 INPP5E Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.312 INPP5E Eleanor Williams Gene: inpp5e has been removed from the panel.
Limb disorders v0.311 IFT80 Eleanor Williams Marked gene: IFT80 as ready
Limb disorders v0.311 IFT80 Eleanor Williams Gene: ift80 has been removed from the panel.
Limb disorders v0.311 IFT80 Eleanor Williams Classified gene: IFT80 as No list
Limb disorders v0.311 IFT80 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.311 IFT80 Eleanor Williams Gene: ift80 has been removed from the panel.
Limb disorders v0.310 IFT52 Eleanor Williams Classified gene: IFT52 as No list
Limb disorders v0.310 IFT52 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.310 IFT52 Eleanor Williams Gene: ift52 has been removed from the panel.
Limb disorders v0.309 IFT172 Eleanor Williams Marked gene: IFT172 as ready
Limb disorders v0.309 IFT172 Eleanor Williams Gene: ift172 has been removed from the panel.
Limb disorders v0.309 IFT172 Eleanor Williams Classified gene: IFT172 as No list
Limb disorders v0.309 IFT172 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.309 IFT172 Eleanor Williams Gene: ift172 has been removed from the panel.
Limb disorders v0.308 IFT140 Eleanor Williams Marked gene: IFT140 as ready
Limb disorders v0.308 IFT140 Eleanor Williams Gene: ift140 has been removed from the panel.
Limb disorders v0.308 IFT140 Eleanor Williams Classified gene: IFT140 as No list
Limb disorders v0.308 IFT140 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.308 IFT140 Eleanor Williams Gene: ift140 has been removed from the panel.
Limb disorders v0.307 ICK Eleanor Williams Classified gene: ICK as No list
Limb disorders v0.307 ICK Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.307 ICK Eleanor Williams Gene: ick has been removed from the panel.
Limb disorders v0.306 HYLS1 Eleanor Williams Marked gene: HYLS1 as ready
Limb disorders v0.306 HYLS1 Eleanor Williams Gene: hyls1 has been removed from the panel.
Limb disorders v0.306 HYLS1 Eleanor Williams Classified gene: HYLS1 as No list
Limb disorders v0.306 HYLS1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.306 HYLS1 Eleanor Williams Gene: hyls1 has been removed from the panel.
Limb disorders v0.305 EVC2 Eleanor Williams Marked gene: EVC2 as ready
Limb disorders v0.305 EVC2 Eleanor Williams Gene: evc2 has been removed from the panel.
Limb disorders v0.305 EVC2 Eleanor Williams Classified gene: EVC2 as No list
Limb disorders v0.305 EVC2 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.305 EVC2 Eleanor Williams Gene: evc2 has been removed from the panel.
Limb disorders v0.304 EVC Eleanor Williams Marked gene: EVC as ready
Limb disorders v0.304 EVC Eleanor Williams Gene: evc has been removed from the panel.
Limb disorders v0.304 EVC Eleanor Williams Classified gene: EVC as No list
Limb disorders v0.304 EVC Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.304 EVC Eleanor Williams Gene: evc has been removed from the panel.
Limb disorders v0.303 DYNC2LI1 Eleanor Williams Marked gene: DYNC2LI1 as ready
Limb disorders v0.303 DYNC2LI1 Eleanor Williams Gene: dync2li1 has been removed from the panel.
Limb disorders v0.303 DYNC2LI1 Eleanor Williams Classified gene: DYNC2LI1 as No list
Limb disorders v0.303 DYNC2LI1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.303 DYNC2LI1 Eleanor Williams Gene: dync2li1 has been removed from the panel.
Limb disorders v0.302 DYNC2H1 Eleanor Williams Classified gene: DYNC2H1 as No list
Limb disorders v0.302 DYNC2H1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.302 DYNC2H1 Eleanor Williams Gene: dync2h1 has been removed from the panel.
Limb disorders v0.301 DDX59 Eleanor Williams Classified gene: DDX59 as No list
Limb disorders v0.301 DDX59 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.301 DDX59 Eleanor Williams Gene: ddx59 has been removed from the panel.
Limb disorders v0.300 CSPP1 Eleanor Williams Marked gene: CSPP1 as ready
Limb disorders v0.300 CSPP1 Eleanor Williams Gene: cspp1 has been removed from the panel.
Limb disorders v0.300 CSPP1 Eleanor Williams Classified gene: CSPP1 as No list
Limb disorders v0.300 CSPP1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.300 CSPP1 Eleanor Williams Gene: cspp1 has been removed from the panel.
Limb disorders v0.299 CEP41 Eleanor Williams Marked gene: CEP41 as ready
Limb disorders v0.299 CEP41 Eleanor Williams Gene: cep41 has been removed from the panel.
Limb disorders v0.299 CEP41 Eleanor Williams Classified gene: CEP41 as No list
Limb disorders v0.299 CEP41 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.299 CEP41 Eleanor Williams Gene: cep41 has been removed from the panel.
Limb disorders v0.298 CEP290 Eleanor Williams Marked gene: CEP290 as ready
Limb disorders v0.298 CEP290 Eleanor Williams Gene: cep290 has been removed from the panel.
Limb disorders v0.298 CEP290 Eleanor Williams Classified gene: CEP290 as No list
Limb disorders v0.298 CEP290 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.298 CEP290 Eleanor Williams Gene: cep290 has been removed from the panel.
Limb disorders v0.297 CEP164 Eleanor Williams Marked gene: CEP164 as ready
Limb disorders v0.297 CEP164 Eleanor Williams Gene: cep164 has been removed from the panel.
Limb disorders v0.297 CEP164 Eleanor Williams Classified gene: CEP164 as No list
Limb disorders v0.297 CEP164 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.297 CEP164 Eleanor Williams Gene: cep164 has been removed from the panel.
Limb disorders v0.296 CEP120 Eleanor Williams Marked gene: CEP120 as ready
Limb disorders v0.296 CEP120 Eleanor Williams Gene: cep120 has been removed from the panel.
Limb disorders v0.296 CEP120 Eleanor Williams Classified gene: CEP120 as No list
Limb disorders v0.296 CEP120 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.296 CEP120 Eleanor Williams Gene: cep120 has been removed from the panel.
Limb disorders v0.295 CENPF Eleanor Williams Marked gene: CENPF as ready
Limb disorders v0.295 CENPF Eleanor Williams Gene: cenpf has been removed from the panel.
Limb disorders v0.295 CENPF Eleanor Williams Classified gene: CENPF as No list
Limb disorders v0.295 CENPF Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.295 CENPF Eleanor Williams Gene: cenpf has been removed from the panel.
Limb disorders v0.294 CC2D2A Eleanor Williams Marked gene: CC2D2A as ready
Limb disorders v0.294 CC2D2A Eleanor Williams Gene: cc2d2a has been removed from the panel.
Limb disorders v0.294 CC2D2A Eleanor Williams Classified gene: CC2D2A as No list
Limb disorders v0.294 CC2D2A Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.294 CC2D2A Eleanor Williams Gene: cc2d2a has been removed from the panel.
Limb disorders v0.293 C5orf42 Eleanor Williams Marked gene: C5orf42 as ready
Limb disorders v0.293 C5orf42 Eleanor Williams Gene: c5orf42 has been removed from the panel.
Limb disorders v0.293 C5orf42 Eleanor Williams Classified gene: C5orf42 as No list
Limb disorders v0.293 C5orf42 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.293 C5orf42 Eleanor Williams Gene: c5orf42 has been removed from the panel.
Limb disorders v0.292 C2CD3 Eleanor Williams Marked gene: C2CD3 as ready
Limb disorders v0.292 C2CD3 Eleanor Williams Gene: c2cd3 has been removed from the panel.
Limb disorders v0.292 C2CD3 Eleanor Williams Classified gene: C2CD3 as No list
Limb disorders v0.292 C2CD3 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.292 C2CD3 Eleanor Williams Gene: c2cd3 has been removed from the panel.
Limb disorders v0.291 BBS9 Eleanor Williams Marked gene: BBS9 as ready
Limb disorders v0.291 BBS9 Eleanor Williams Gene: bbs9 has been removed from the panel.
Limb disorders v0.291 BBS9 Eleanor Williams Classified gene: BBS9 as No list
Limb disorders v0.291 BBS9 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.291 BBS9 Eleanor Williams Gene: bbs9 has been removed from the panel.
Limb disorders v0.290 BBS7 Eleanor Williams Marked gene: BBS7 as ready
Limb disorders v0.290 BBS7 Eleanor Williams Gene: bbs7 has been removed from the panel.
Limb disorders v0.290 BBS7 Eleanor Williams Classified gene: BBS7 as No list
Limb disorders v0.290 BBS7 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.290 BBS7 Eleanor Williams Gene: bbs7 has been removed from the panel.
Limb disorders v0.289 BBS5 Eleanor Williams Marked gene: BBS5 as ready
Limb disorders v0.289 BBS5 Eleanor Williams Gene: bbs5 has been removed from the panel.
Limb disorders v0.289 BBS5 Eleanor Williams Classified gene: BBS5 as No list
Limb disorders v0.289 BBS5 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.289 BBS5 Eleanor Williams Gene: bbs5 has been removed from the panel.
Limb disorders v0.288 BBS4 Eleanor Williams Marked gene: BBS4 as ready
Limb disorders v0.288 BBS4 Eleanor Williams Gene: bbs4 has been removed from the panel.
Limb disorders v0.288 BBS4 Eleanor Williams Classified gene: BBS4 as No list
Limb disorders v0.288 BBS4 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.288 BBS4 Eleanor Williams Gene: bbs4 has been removed from the panel.
Limb disorders v0.287 BBS2 Eleanor Williams Marked gene: BBS2 as ready
Limb disorders v0.287 BBS2 Eleanor Williams Gene: bbs2 has been removed from the panel.
Limb disorders v0.287 BBS2 Eleanor Williams Classified gene: BBS2 as No list
Limb disorders v0.287 BBS2 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.287 BBS2 Eleanor Williams Gene: bbs2 has been removed from the panel.
Limb disorders v0.286 BBS12 Eleanor Williams Marked gene: BBS12 as ready
Limb disorders v0.286 BBS12 Eleanor Williams Gene: bbs12 has been removed from the panel.
Limb disorders v0.286 BBS12 Eleanor Williams Classified gene: BBS12 as No list
Limb disorders v0.286 BBS12 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.286 BBS12 Eleanor Williams Gene: bbs12 has been removed from the panel.
Limb disorders v0.285 BBS10 Eleanor Williams Marked gene: BBS10 as ready
Limb disorders v0.285 BBS10 Eleanor Williams Gene: bbs10 has been removed from the panel.
Limb disorders v0.285 BBS10 Eleanor Williams Classified gene: BBS10 as No list
Limb disorders v0.285 BBS10 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.285 BBS10 Eleanor Williams Gene: bbs10 has been removed from the panel.
Limb disorders v0.284 BBS1 Eleanor Williams Classified gene: BBS1 as No list
Limb disorders v0.284 BBS1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.284 BBS1 Eleanor Williams Gene: bbs1 has been removed from the panel.
Limb disorders v0.283 B9D2 Eleanor Williams Classified gene: B9D2 as No list
Limb disorders v0.283 B9D2 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.283 B9D2 Eleanor Williams Gene: b9d2 has been removed from the panel.
Limb disorders v0.282 ARL6 Eleanor Williams Classified gene: ARL6 as No list
Limb disorders v0.282 ARL6 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.282 ARL6 Eleanor Williams Gene: arl6 has been removed from the panel.
Limb disorders v0.281 ALMS1 Eleanor Williams Classified gene: ALMS1 as No list
Limb disorders v0.281 ALMS1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.281 ALMS1 Eleanor Williams Gene: alms1 has been removed from the panel.
Limb disorders v0.280 AHI1 Eleanor Williams Classified gene: AHI1 as No list
Limb disorders v0.280 AHI1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.280 AHI1 Eleanor Williams Gene: ahi1 has been removed from the panel.
Limb disorders v0.279 GLI3 Eleanor Williams Marked gene: GLI3 as ready
Limb disorders v0.279 GLI3 Eleanor Williams Gene: gli3 has been classified as Green List (High Evidence).
Limb disorders v0.279 GLI3 Eleanor Williams Classified gene: GLI3 as Green List (high evidence)
Limb disorders v0.279 GLI3 Eleanor Williams Added comment: Comment on list classification: Keeping this gene green on the Limb disorders panel, although it is also green on the Rare multisystem ciliopathies panel, on advice of Genomics England clinical team.
Limb disorders v0.279 GLI3 Eleanor Williams Gene: gli3 has been classified as Green List (High Evidence).
Limb disorders v0.278 TCTEX1D2 Eleanor Williams Source Expert Review Removed was added to TCTEX1D2.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Limb disorders v0.278 WDR34 Eleanor Williams Source Expert Review Removed was added to WDR34.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 DDX59 Eleanor Williams Source Expert Review Removed was added to DDX59.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 WDR35 Eleanor Williams Source Expert Review Removed was added to WDR35.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 WDPCP Eleanor Williams Source Expert Review Removed was added to WDPCP.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 WDR19 Eleanor Williams Source Expert Review Removed was added to WDR19.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TCTN3 Eleanor Williams Source Expert Review Removed was added to TCTN3.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 B9D2 Eleanor Williams Source Expert Review Removed was added to B9D2.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 AHI1 Eleanor Williams Source Expert Review Removed was added to AHI1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TCTN2 Eleanor Williams Source Expert Review Removed was added to TCTN2.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 BBS1 Eleanor Williams Source Expert Review Removed was added to BBS1.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 ARL6 Eleanor Williams Source Expert Review Removed was added to ARL6.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 ALMS1 Eleanor Williams Source Expert Review Removed was added to ALMS1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 CENPF Eleanor Williams Source Expert Review Removed was added to CENPF.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 DYNC2LI1 Eleanor Williams Source Expert Review Removed was added to DYNC2LI1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 IFT140 Eleanor Williams Source Expert Review Removed was added to IFT140.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 NEK1 Eleanor Williams Source Expert Review Removed was added to NEK1.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 DYNC2H1 Eleanor Williams Source Expert Review Removed was added to DYNC2H1.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 IFT80 Eleanor Williams Source Expert Review Removed was added to IFT80.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 IFT52 Eleanor Williams Source Expert Review Removed was added to IFT52.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Limb disorders v0.278 CEP120 Eleanor Williams Source Expert Review Removed was added to CEP120.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TRAF3IP1 Eleanor Williams Source Expert Review Removed was added to TRAF3IP1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 IFT172 Eleanor Williams Source Expert Review Removed was added to IFT172.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 NPHP3 Eleanor Williams Source Expert Review Removed was added to NPHP3.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 ICK Eleanor Williams Source Expert Review Removed was added to ICK.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 ZSWIM6 Eleanor Williams Source Expert Review Removed was added to ZSWIM6.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Limb disorders v0.278 C2CD3 Eleanor Williams Source Expert Review Removed was added to C2CD3.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TTC21B Eleanor Williams Source Expert Review Removed was added to TTC21B.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 CEP164 Eleanor Williams Source Expert Review Removed was added to CEP164.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TMEM67 Eleanor Williams Source Expert Review Removed was added to TMEM67.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 TMEM216 Eleanor Williams Source Expert Review Removed was added to TMEM216.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 KIAA0586 Eleanor Williams Source Expert Review Removed was added to KIAA0586.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 C5orf42 Eleanor Williams Source Expert Review Removed was added to C5orf42.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 RPGRIP1L Eleanor Williams Source Expert Review Removed was added to RPGRIP1L.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 CSPP1 Eleanor Williams Source Expert Review Removed was added to CSPP1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TMEM237 Eleanor Williams Source Expert Review Removed was added to TMEM237.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 INPP5E Eleanor Williams Source Expert Review Removed was added to INPP5E.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TMEM138 Eleanor Williams Source Expert Review Removed was added to TMEM138.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 CC2D2A Eleanor Williams Source Expert Review Removed was added to CC2D2A.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 TMEM231 Eleanor Williams Source Expert Review Removed was added to TMEM231.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 CEP41 Eleanor Williams Source Expert Review Removed was added to CEP41.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 KIF7 Eleanor Williams Source Expert Review Removed was added to KIF7.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 OFD1 Eleanor Williams Source Expert Review Removed was added to OFD1.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 HYLS1 Eleanor Williams Source Expert Review Removed was added to HYLS1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 CEP290 Eleanor Williams Source Expert Review Removed was added to CEP290.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 EVC2 Eleanor Williams Source Expert Review Removed was added to EVC2.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 EVC Eleanor Williams Source Expert Review Removed was added to EVC.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 SDCCAG8 Eleanor Williams Source Expert Review Removed was added to SDCCAG8.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 MKS1 Eleanor Williams Source Expert Review Removed was added to MKS1.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 BBS9 Eleanor Williams Source Expert Review Removed was added to BBS9.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TTC8 Eleanor Williams Source Expert Review Removed was added to TTC8.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS7 Eleanor Williams Source Expert Review Removed was added to BBS7.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 MKKS Eleanor Williams Source Expert Review Removed was added to MKKS.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS5 Eleanor Williams Source Expert Review Removed was added to BBS5.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS4 Eleanor Williams Source Expert Review Removed was added to BBS4.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS2 Eleanor Williams Source Expert Review Removed was added to BBS2.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS12 Eleanor Williams Source Expert Review Removed was added to BBS12.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS10 Eleanor Williams Source Expert Review Removed was added to BBS10.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.276 PROM1 Eleanor Williams Marked gene: PROM1 as ready
Limb disorders v0.276 PROM1 Eleanor Williams Added comment: Comment when marking as ready: No evidence that this gene is associated with a limb phenotype.
Limb disorders v0.276 PROM1 Eleanor Williams Gene: prom1 has been classified as Red List (Low Evidence).
Limb disorders v0.276 PROM1 Eleanor Williams commented on gene: PROM1
Limb disorders v0.276 PNPLA6 Eleanor Williams Marked gene: PNPLA6 as ready
Limb disorders v0.276 PNPLA6 Eleanor Williams Added comment: Comment when marking as ready: No evidence that this gene is associated with limb disorders.
Limb disorders v0.276 PNPLA6 Eleanor Williams Gene: pnpla6 has been classified as Red List (Low Evidence).
Limb disorders v0.276 PNPLA6 Eleanor Williams commented on gene: PNPLA6
Limb disorders v0.276 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Limb disorders v0.275 TWIST1 Eleanor Williams Marked gene: TWIST1 as ready
Limb disorders v0.275 TWIST1 Eleanor Williams Gene: twist1 has been classified as Green List (High Evidence).
Limb disorders v0.275 TRIM32 Eleanor Williams Marked gene: TRIM32 as ready
Limb disorders v0.275 TRIM32 Eleanor Williams Gene: trim32 has been classified as Red List (Low Evidence).
Limb disorders v0.275 TRAPPC2 Eleanor Williams Marked gene: TRAPPC2 as ready
Limb disorders v0.275 TRAPPC2 Eleanor Williams Gene: trappc2 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.275 SOX9 Eleanor Williams Marked gene: SOX9 as ready
Limb disorders v0.275 SOX9 Eleanor Williams Gene: sox9 has been classified as Red List (Low Evidence).
Limb disorders v0.275 SLC25A21 Eleanor Williams Marked gene: SLC25A21 as ready
Limb disorders v0.275 SLC25A21 Eleanor Williams Gene: slc25a21 has been classified as Red List (Low Evidence).
Limb disorders v0.275 SHH Eleanor Williams Marked gene: SHH as ready
Limb disorders v0.275 SHH Eleanor Williams Gene: shh has been classified as Red List (Low Evidence).
Limb disorders v0.275 ZNF141 Eleanor Williams Marked gene: ZNF141 as ready
Limb disorders v0.275 ZNF141 Eleanor Williams Gene: znf141 has been classified as Red List (Low Evidence).
Limb disorders v0.275 USP9X Eleanor Williams Marked gene: USP9X as ready
Limb disorders v0.275 USP9X Eleanor Williams Gene: usp9x has been classified as Green List (High Evidence).
Limb disorders v0.275 RAD51C Eleanor Williams Classified gene: RAD51C as Amber List (moderate evidence)
Limb disorders v0.275 RAD51C Eleanor Williams Added comment: Comment on list classification: 2 cases reported
Limb disorders v0.275 RAD51C Eleanor Williams Gene: rad51c has been classified as Amber List (Moderate Evidence).
Limb disorders v0.274 PIK3R2 Eleanor Williams Marked gene: PIK3R2 as ready
Limb disorders v0.274 PIK3R2 Eleanor Williams Gene: pik3r2 has been classified as Green List (High Evidence).
Limb disorders v0.274 PIK3R2 Eleanor Williams Mode of pathogenicity for gene: PIK3R2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Limb disorders v0.273 PIK3CA Eleanor Williams Marked gene: PIK3CA as ready
Limb disorders v0.273 PIK3CA Eleanor Williams Gene: pik3ca has been classified as Green List (High Evidence).
Limb disorders v0.273 PIK3CA Eleanor Williams Mode of pathogenicity for gene: PIK3CA was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Limb disorders v0.272 PDE6D Eleanor Williams Marked gene: PDE6D as ready
Limb disorders v0.272 PDE6D Eleanor Williams Gene: pde6d has been classified as Red List (Low Evidence).
Limb disorders v0.272 MEGF8 Eleanor Williams Marked gene: MEGF8 as ready
Limb disorders v0.272 MEGF8 Eleanor Williams Gene: megf8 has been classified as Green List (High Evidence).
Limb disorders v0.272 MBTPS2 Eleanor Williams Marked gene: MBTPS2 as ready
Limb disorders v0.272 MBTPS2 Eleanor Williams Gene: mbtps2 has been classified as Red List (Low Evidence).
Limb disorders v0.272 LZTFL1 Eleanor Williams Marked gene: LZTFL1 as ready
Limb disorders v0.272 LZTFL1 Eleanor Williams Gene: lztfl1 has been classified as Green List (High Evidence).
Limb disorders v0.272 LBR Eleanor Williams Marked gene: LBR as ready
Limb disorders v0.272 LBR Eleanor Williams Gene: lbr has been classified as Green List (High Evidence).
Limb disorders v0.272 IFT52 Eleanor Williams Marked gene: IFT52 as ready
Limb disorders v0.272 IFT52 Eleanor Williams Gene: ift52 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.272 IFT27 Eleanor Williams Marked gene: IFT27 as ready
Limb disorders v0.272 IFT27 Eleanor Williams Gene: ift27 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.272 ICK Eleanor Williams Marked gene: ICK as ready
Limb disorders v0.272 ICK Eleanor Williams Gene: ick has been classified as Green List (High Evidence).
Limb disorders v0.272 GRIP1 Eleanor Williams Marked gene: GRIP1 as ready
Limb disorders v0.272 GRIP1 Eleanor Williams Gene: grip1 has been classified as Green List (High Evidence).
Limb disorders v0.272 GREM1 Eleanor Williams Marked gene: GREM1 as ready
Limb disorders v0.272 GREM1 Eleanor Williams Gene: grem1 has been classified as Red List (Low Evidence).
Limb disorders v0.272 GPC3 Eleanor Williams Marked gene: GPC3 as ready
Limb disorders v0.272 GPC3 Eleanor Williams Gene: gpc3 has been classified as Green List (High Evidence).
Limb disorders v0.272 GLI2 Eleanor Williams Marked gene: GLI2 as ready
Limb disorders v0.272 GLI2 Eleanor Williams Gene: gli2 has been classified as Green List (High Evidence).
Limb disorders v0.272 FREM2 Eleanor Williams Marked gene: FREM2 as ready
Limb disorders v0.272 FREM2 Eleanor Williams Gene: frem2 has been classified as Green List (High Evidence).
Limb disorders v0.272 FRAS1 Eleanor Williams Marked gene: FRAS1 as ready
Limb disorders v0.272 FRAS1 Eleanor Williams Gene: fras1 has been classified as Green List (High Evidence).
Limb disorders v0.272 FMN1 Eleanor Williams Marked gene: FMN1 as ready
Limb disorders v0.272 FMN1 Eleanor Williams Gene: fmn1 has been classified as Red List (Low Evidence).
Limb disorders v0.272 FGF9 Eleanor Williams Marked gene: FGF9 as ready
Limb disorders v0.272 FGF9 Eleanor Williams Gene: fgf9 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.272 FGD1 Eleanor Williams Marked gene: FGD1 as ready
Limb disorders v0.272 FGD1 Eleanor Williams Gene: fgd1 has been classified as Green List (High Evidence).
Limb disorders v0.272 FBLN1 Eleanor Williams Marked gene: FBLN1 as ready
Limb disorders v0.272 FBLN1 Eleanor Williams Gene: fbln1 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.272 FANCM Eleanor Williams Marked gene: FANCM as ready
Limb disorders v0.272 FANCM Eleanor Williams Gene: fancm has been classified as Red List (Low Evidence).
Limb disorders v0.272 EBP Eleanor Williams Marked gene: EBP as ready
Limb disorders v0.272 EBP Eleanor Williams Gene: ebp has been classified as Green List (High Evidence).
Limb disorders v0.272 DLX6 Eleanor Williams Marked gene: DLX6 as ready
Limb disorders v0.272 DLX6 Eleanor Williams Gene: dlx6 has been classified as Red List (Low Evidence).
Limb disorders v0.272 ZNF141 Eleanor Williams Tag watchlist tag was added to gene: ZNF141.
Limb disorders v0.272 GREM1 Eleanor Williams Tag watchlist tag was added to gene: GREM1.
Limb disorders v0.272 LZTFL1 Eleanor Williams Source Expert Review Green was added to LZTFL1.
Mode of inheritance for gene LZTFL1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Bardet-Biedl syndrome 17 615994 for gene: LZTFL1
Publications for gene LZTFL1 were changed from to 22510444; 23692385
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.272 LBR Eleanor Williams Source Expert Review Green was added to LBR.
Mode of inheritance for gene LBR was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes mesomelia; Greenberg skeletal dysplasia, 215140; rhizomelia; post-axial polydactyly; Polydactyly for gene: LBR
Publications for gene LBR were changed from to 18382993; 12618959; 21327084; 12118250
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.272 ICK Eleanor Williams Source Expert Review Green was added to ICK.
Mode of inheritance for gene ICK was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes ECO; Rhizomelia; Short-rib thoracic dysplasia with polydactyly; Polydactyly; SRTD; Mesomelia; Endocrine-cerebroosteodysplasia, 612651 for gene: ICK
Publications for gene ICK were changed from to 27466187; 27069622; 19185282
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.272 GRIP1 Eleanor Williams Source Expert Review Green was added to GRIP1.
Mode of inheritance for gene GRIP1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fraser syndrome 3 617667 for gene: GRIP1
Publications for gene GRIP1 were changed from to 22510445; 24357607
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.272 GPC3 Eleanor Williams Source Expert Review Green was added to GPC3.
Mode of inheritance for gene GPC3 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Added phenotypes Simpson-Golabi-Behmel syndrome, type 1 312870 for gene: GPC3
Publications for gene GPC3 were changed from to 10814714
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.272 GLI2 Eleanor Williams Source Expert Review Green was added to GLI2.
Mode of inheritance for gene GLI2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Holoprosencephaly 9 610829; Culler-Jones syndrome 615849 for gene: GLI2
Publications for gene GLI2 were changed from to 21204792; 14581620
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.272 FREM2 Eleanor Williams Source Expert Review Green was added to FREM2.
Mode of inheritance for gene FREM2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fraser syndrome 2 617666 for gene: FREM2
Publications for gene FREM2 were changed from to 18203166; 18671281; 15838507
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.272 FRAS1 Eleanor Williams Source Expert Review Green was added to FRAS1.
Mode of inheritance for gene FRAS1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fraser syndrome 1 219000 for gene: FRAS1
Publications for gene FRAS1 were changed from to 12766769; 17163535; 16894541
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.272 FGD1 Eleanor Williams Source Expert Review Green was added to FGD1.
Mode of inheritance for gene FGD1 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Added phenotypes Aarskog-Scott syndrome 305400 for gene: FGD1
Publications for gene FGD1 were changed from 15809997 to 14560308; 20082460; 17152066; 11093277; 7954831; 10930571; 15809997
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v0.272 EBP Eleanor Williams Source Expert Review Green was added to EBP.
Mode of inheritance for gene EBP was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Added phenotypes Polydactyly; Chondrodysplasia punctata, X-linked dominant 302960 for gene: EBP
Publications for gene EBP were changed from to 10942423; 10391218; 10391219; 12509714
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.272 DDX59 Eleanor Williams Added phenotypes Orofaciodigital syndrome V 174300 for gene: DDX59
Publications for gene DDX59 were changed from 23972372; 28711741; 29127725 to 29127725; 28711741; 23972372
Rating Changed from Green List (high evidence) to Green List (high evidence)
Limb disorders v0.272 UBE3B Eleanor Williams Source Expert Review Amber was added to UBE3B.
Mode of inheritance for gene UBE3B was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Kaufman oculocerebrofacial syndrome 244450 for gene: UBE3B
Publications for gene UBE3B were changed from to 23200864
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Limb disorders v0.272 TRAPPC2 Eleanor Williams Added phenotypes Spondyloepiphyseal dysplasia tarda, 313400 for gene: TRAPPC2
Limb disorders v0.272 IFT52 Eleanor Williams Source Expert Review Amber was added to IFT52.
Mode of inheritance for gene IFT52 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Short-rib thoracic dysplasia 16 with or without polydactyly, 617102; Polydactyly for gene: IFT52
Publications for gene IFT52 were changed from to 26880018
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Limb disorders v0.272 IFT27 Eleanor Williams Source Expert Review Amber was added to IFT27.
Mode of inheritance for gene IFT27 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes ?Bardet-Biedl syndrome 19, 615996; Polydactyly for gene: IFT27
Publications for gene IFT27 were changed from to 24488770; 29704304
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Limb disorders v0.272 FGF9 Eleanor Williams Added phenotypes Multiple synostoses syndrome 3 612961 for gene: FGF9
Publications for gene FGF9 were changed from 19460469; 28169396; 19589401 to 19460469; 28730625; 28169396; 19589401
Limb disorders v0.272 FBLN1 Eleanor Williams Added phenotypes Synpolydactyly, 3/3'4, associated with metacarpal and metatarsal synostoses 608180; SYNPOLYDACTYLY, 3/3-PRIME/4, ASSOCIATED WITH METACARPAL AND METATARSAL SYNOSTOSES for gene: FBLN1
Publications for gene FBLN1 were changed from 24084572; 11836357 to 11836357; 24084572
Limb disorders v0.271 RBM10 Eleanor Williams Mode of inheritance for gene RBM10 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Added phenotypes TARP syndrome 311900 for gene: RBM10
Publications for gene RBM10 were changed from to 21910224; 20451169; 24259342
Limb disorders v0.271 RAD51C Eleanor Williams Mode of inheritance for gene RAD51C was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group O 613390 for gene: RAD51C
Publications for gene RAD51C were changed from to 20400963; 29278735
Limb disorders v0.271 PROM1 Eleanor Williams Source Expert Review Red was added to PROM1.
Mode of inheritance for gene PROM1 was changed from to Unknown
Limb disorders v0.271 PNPLA6 Eleanor Williams Source Expert Review Red was added to PNPLA6.
Mode of inheritance for gene PNPLA6 was changed from to Unknown
Limb disorders v0.271 HNRNPK Eleanor Williams Source Expert Review Amber was added to HNRNPK.
Added phenotypes Au-Kline syndrome 616580 for gene: HNRNPK
Publications for gene HNRNPK were changed from to 26173930; 19477957
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Limb disorders v0.271 GATA1 Eleanor Williams Source Expert Review Amber was added to GATA1.
Mode of inheritance for gene GATA1 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Added phenotypes Radial Ray abnormality for gene: GATA1
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Limb disorders v0.271 ZNF141 Eleanor Williams Source Expert Review Red was added to ZNF141.
Added phenotypes ?Polydactyly, postaxial, type A6 615226; Polydactyly for gene: ZNF141
Limb disorders v0.271 TRIM32 Eleanor Williams Source Expert Review Red was added to TRIM32.
Mode of inheritance for gene TRIM32 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Bardet-Biedl syndrome 11, 615988; Polydactyly for gene: TRIM32
Publications for gene TRIM32 were changed from to 20301537; 16606853
Limb disorders v0.271 SOX9 Eleanor Williams Source Expert Review Red was added to SOX9.
Mode of inheritance for gene SOX9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Brachydactyly-anonychia for gene: SOX9
Publications for gene SOX9 were changed from 19639023 to 24704791; 19639023
Limb disorders v0.271 SLC25A21 Eleanor Williams Added phenotypes Familial synpolydactyly of the hands and feet for gene: SLC25A21
Publications for gene SLC25A21 were changed from 25759628 to 22011226; 25759628; 14504231
Limb disorders v0.271 SHH Eleanor Williams Mode of inheritance for gene SHH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Preaxial polydactyly; Polydactyly for gene: SHH
Publications for gene SHH were changed from 12032320; 12837695; 25782671 to 25782671; 12837695; 12032320
Limb disorders v0.271 SEM1 Eleanor Williams Source Expert Review Red was added to SEM1.
Added phenotypes Split hand/foot malformation 1, 183600 for gene: SEM1
Limb disorders v0.271 PDE6D Eleanor Williams Source Expert Review Red was added to PDE6D.
Mode of inheritance for gene PDE6D was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes ?Joubert syndrome 22 615665 for gene: PDE6D
Publications for gene PDE6D were changed from to 24166846
Limb disorders v0.271 MBTPS2 Eleanor Williams Source Expert Review Red was added to MBTPS2.
Mode of inheritance for gene MBTPS2 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Added phenotypes IFAP syndrome with or without BRESHECK syndrome 308205 for gene: MBTPS2
Publications for gene MBTPS2 were changed from to 9021007
Limb disorders v0.271 GREM1 Eleanor Williams Source Expert Review Red was added to GREM1.
Mode of inheritance for gene GREM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene GREM1 were changed from 20610440 to 26527308; 22888807; 16908629; 15201225; 20610440; 22965740
Limb disorders v0.271 FMN1 Eleanor Williams Source Expert Review Red was added to FMN1.
Publications for gene FMN1 were changed from to 20610440
Limb disorders v0.271 FANCM Eleanor Williams Source Expert Review Red was added to FANCM.
Added phenotypes Radial Ray abnormality for gene: FANCM
Publications for gene FANCM were changed from to 28837162
Limb disorders v0.271 DLX6 Eleanor Williams Source Expert Review Red was added to DLX6.
Mode of inheritance for gene DLX6 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Split hand/foot malformation 1 for gene: DLX6
Publications for gene DLX6 were changed from to 28611547
Limb disorders v0.271 USP9X Eleanor Williams Source Expert Review Green was added to USP9X.
Mode of inheritance for gene USP9X was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Added phenotypes Mental retardation, X-linked 99, syndromic, female-restricted for gene: USP9X
Publications for gene USP9X were changed from to 26833328
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.271 TWIST1 Eleanor Williams Source Expert Review Green was added to TWIST1.
Mode of inheritance for gene TWIST1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Robinow-Sorauf syndrome, 180750; Saethre-Chotzen syndrome, 101400; Polydactyly for gene: TWIST1
Publications for gene TWIST1 were changed from to 11754069; 12791045; 16251895; 10465122; 30152628; 9792856; 11977182; 25565733; 9585583
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.271 PIK3R2 Eleanor Williams Source Expert Review Green was added to PIK3R2.
Mode of inheritance for gene PIK3R2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 603387 for gene: PIK3R2
Publications for gene PIK3R2 were changed from to 23745724; 22729224; 26520804
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.271 PIK3CA Eleanor Williams Source Expert Review Green was added to PIK3CA.
Mode of inheritance for gene PIK3CA was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Macrodactyly, somatic 155500; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic 602501; CLOVE syndrome, somatic 612918; CLAPO syndrome, somatic 613089 for gene: PIK3CA
Publications for gene PIK3CA were changed from to 23100325; 19353582; 29446767; 22729224; 19011570
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.271 MEGF8 Eleanor Williams Source Expert Review Green was added to MEGF8.
Mode of inheritance for gene MEGF8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Carpenter syndrome 2 614976 for gene: MEGF8
Publications for gene MEGF8 were changed from to 23063620
Rating Changed from Red List (low evidence) to Green List (high evidence)
Limb disorders v0.270 TWIST1 Louise Daugherty reviewed gene: TWIST1: Rating: GREEN; Mode of pathogenicity: ; Publications: 10465122, 11754069, 11977182, 9585583, 9792856, 16251895, 30152628, 12791045, 10465122, 25565733; Phenotypes: Polydactyly, Robinow-Sorauf syndrome, 180750, Saethre-Chotzen syndrome, 101400 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.270 TRIM32 Louise Daugherty reviewed gene: TRIM32: Rating: RED; Mode of pathogenicity: ; Publications: 16606853, 20301537; Phenotypes: Polydactyly, Bardet-Biedl syndrome 11, 615988; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 TRAPPC2 Louise Daugherty reviewed gene: TRAPPC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondyloepiphyseal dysplasia tarda, 313400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Limb disorders v0.270 SOX9 Louise Daugherty reviewed gene: SOX9: Rating: RED; Mode of pathogenicity: ; Publications: 19639023, 24704791; Phenotypes: Brachydactyly-anonychia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.270 SLC25A21 Louise Daugherty reviewed gene: SLC25A21: Rating: RED; Mode of pathogenicity: ; Publications: 25759628, 14504231, 22011226; Phenotypes: Familial synpolydactyly of the hands and feet; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.270 SHH Louise Daugherty reviewed gene: SHH: Rating: RED; Mode of pathogenicity: ; Publications: 12032320, 12837695, 25782671; Phenotypes: Preaxial polydactyly, Polydactyly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb disorders v0.270 SEM1 Louise Daugherty edited their review of gene: SEM1: Added comment: Agree with Red rating,Originally submitted as DSS1 by external reviewer (not SHFM1), the new HGNC-approved symbol is SEM1. Although Split-hand/foot malformation-1 (disease acronym and previous gene symbol SHFM1) is a relevant phenotype to the Limb panel, Split-hand/foot malformation-1 represents a contiguous gene syndrome caused by deletion, duplication, or rearrangement of chromosome 7q21.3 involving the DSS1 (new gene symbol SEM1), DLX5, and DLX6 genes and possible regulatory elements in the region. Evidence exists that SHFM1 can also be caused by heterozygous mutation in the DLX5 gene. This is not a monogeneic disorder.; Changed phenotypes: Split hand/foot malformation 1, 183600; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.270 ZNF141 Ellen McDonagh edited their review of gene: ZNF141: Added comment: PMID: 23160277 - family report of a missense variant segregating with autosomal recessive postaxial polydactyly type A. Functional analysis was not carried out to confirm the effect of the missense. Not enough evidence at this time for this gene to be green - added the watchlist tag.; Changed rating: RED; Changed publications: 23160277; Changed phenotypes: ?Polydactyly, postaxial, type A6 615226, Polydactyly; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 USP9X Ellen McDonagh reviewed gene: USP9X: Rating: GREEN; Mode of pathogenicity: ; Publications: 26833328; Phenotypes: Mental retardation, X-linked 99, syndromic, female-restricted ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Limb disorders v0.270 UBE3B Ellen McDonagh reviewed gene: UBE3B: Rating: AMBER; Mode of pathogenicity: ; Publications: 23200864; Phenotypes: Kaufman oculocerebrofacial syndrome 244450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 FMN1 Eleanor Williams reviewed gene: FMN1: Rating: RED; Mode of pathogenicity: ; Publications: 20610440; Phenotypes: ; Mode of inheritance:
Limb disorders v0.270 FGF9 Eleanor Williams edited their review of gene: FGF9: Added comment: No new evidence so keep as Amber; Changed rating: AMBER; Changed publications: 19460469, 28169396, 19589401, 28730625; Changed phenotypes: Multiple synostoses syndrome 3 612961; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.270 FGD1 Eleanor Williams reviewed gene: FGD1: Rating: GREEN; Mode of pathogenicity: ; Publications: 15809997, 7954831, 10930571, 11093277, 14560308, 17152066, 20082460; Phenotypes: Aarskog-Scott syndrome 305400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Limb disorders v0.270 FBLN1 Eleanor Williams reviewed gene: FBLN1: Rating: AMBER; Mode of pathogenicity: ; Publications: 24084572, 11836357; Phenotypes: Synpolydactyly, 3/3'4, associated with metacarpal and metatarsal synostoses 608180, SYNPOLYDACTYLY, 3/3-PRIME/4, ASSOCIATED WITH METACARPAL AND METATARSAL SYNOSTOSES; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb disorders v0.270 FANCM Eleanor Williams reviewed gene: FANCM: Rating: RED; Mode of pathogenicity: ; Publications: 28837162; Phenotypes: Radial Ray abnormality; Mode of inheritance:
Limb disorders v0.270 EBP Eleanor Williams reviewed gene: EBP: Rating: GREEN; Mode of pathogenicity: ; Publications: 10391218, 10391219, 10942423, 12509714; Phenotypes: Polydactyly, Chondrodysplasia punctata, X-linked dominant 302960; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Limb disorders v0.270 DLX6 Eleanor Williams edited their review of gene: DLX6: Changed rating: RED; Changed publications: 28611547; Changed phenotypes: Split hand/foot malformation 1; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.270 DDX59 Eleanor Williams edited their review of gene: DDX59: Added comment: Mutations identified in 5 families. Postaxial polydactyly reported in 4.; Changed rating: GREEN; Changed publications: 23972372, 28711741, 29127725; Changed phenotypes: Orofaciodigital syndrome V 174300; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 RBM10 Eleanor Williams edited their review of gene: RBM10: Changed rating: AMBER; Changed publications: 20451169, 21910224, 24259342; Changed phenotypes: TARP syndrome 311900; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Limb disorders v0.270 RAD51C Sarah Leigh reviewed gene: RAD51C: Rating: AMBER; Mode of pathogenicity: ; Publications: 20400963, 29278735; Phenotypes: Fanconi anemia, complementation group O 613390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 PROM1 Sarah Leigh reviewed gene: PROM1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Limb disorders v0.270 PNPLA6 Sarah Leigh reviewed gene: PNPLA6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Limb disorders v0.270 PIK3R2 Sarah Leigh reviewed gene: PIK3R2: 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: 22729224, 23745724, 26520804; Phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 603387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.270 PIK3CA Sarah Leigh reviewed gene: PIK3CA: 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: 23100325, 29446767, 19011570, 19353582, 22729224; Phenotypes: Macrodactyly, somatic 155500, CLAPO syndrome, somatic 613089, CLOVE syndrome, somatic 612918, Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic 602501; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.270 PDE6D Sarah Leigh reviewed gene: PDE6D: Rating: RED; Mode of pathogenicity: ; Publications: 24166846; Phenotypes: ?Joubert syndrome 22 615665; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 MEGF8 Sarah Leigh reviewed gene: MEGF8: Rating: GREEN; Mode of pathogenicity: ; Publications: 23063620; Phenotypes: Carpenter syndrome 2 614976; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 MBTPS2 Sarah Leigh reviewed gene: MBTPS2: Rating: RED; Mode of pathogenicity: ; Publications: 9021007; Phenotypes: IFAP syndrome with or without BRESHECK syndrome 308205; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Limb disorders v0.270 LZTFL1 Sarah Leigh reviewed gene: LZTFL1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23692385, 22510444; Phenotypes: Bardet-Biedl syndrome 17 615994; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 HNRNPK Ellen McDonagh reviewed gene: HNRNPK: Rating: AMBER; Mode of pathogenicity: ; Publications: 26173930, 19477957; Phenotypes: Au-Kline syndrome 616580; Mode of inheritance:
Limb disorders v0.270 GRIP1 Ellen McDonagh reviewed gene: GRIP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 22510445, 24357607; Phenotypes: Fraser syndrome 3 617667; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 GREM1 Ellen McDonagh reviewed gene: GREM1: Rating: RED; Mode of pathogenicity: ; Publications: 20610440, 26527308, 22888807, 22965740, 15201225, 16908629; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.270 GPC3 Ellen McDonagh reviewed gene: GPC3: Rating: GREEN; Mode of pathogenicity: ; Publications: 10814714; Phenotypes: Simpson-Golabi-Behmel syndrome, type 1 312870; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Limb disorders v0.270 GLI2 Ellen McDonagh reviewed gene: GLI2: Rating: GREEN; Mode of pathogenicity: ; Publications: 14581620, 14581620, 21204792, 21204792; Phenotypes: Culler-Jones syndrome 615849, Holoprosencephaly 9 610829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.270 GATA1 Ellen McDonagh reviewed gene: GATA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Radial Ray abnormality; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Limb disorders v0.270 FREM2 Ellen McDonagh reviewed gene: FREM2: Rating: GREEN; Mode of pathogenicity: ; Publications: 15838507, 18671281, 18203166; Phenotypes: Fraser syndrome 2 617666; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 FRAS1 Ellen McDonagh reviewed gene: FRAS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 12766769, 16894541, 17163535; Phenotypes: Fraser syndrome 1 219000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 LBR Rebecca Foulger reviewed gene: LBR: Rating: GREEN; Mode of pathogenicity: ; Publications: 12618959, 12118250, 18382993, 21327084; Phenotypes: Polydactyly, Greenberg skeletal dysplasia, 215140, rhizomelia, mesomelia, post-axial polydactyly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 IFT52 Rebecca Foulger reviewed gene: IFT52: Rating: AMBER; Mode of pathogenicity: ; Publications: 26880018; Phenotypes: Polydactyly, Short-rib thoracic dysplasia 16 with or without polydactyly, 617102; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 IFT27 Rebecca Foulger reviewed gene: IFT27: Rating: AMBER; Mode of pathogenicity: ; Publications: 24488770, 29704304; Phenotypes: Polydactyly, ?Bardet-Biedl syndrome 19, 615996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.270 ICK Rebecca Foulger reviewed gene: ICK: Rating: GREEN; Mode of pathogenicity: ; Publications: 19185282, 27069622, 27466187; Phenotypes: Polydactyly, Endocrine-cerebroosteodysplasia, 612651, ECO, Short-rib thoracic dysplasia with polydactyly, SRTD, Rhizomelia, Mesomelia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.269 KIAA0586 Eleanor Williams Marked gene: KIAA0586 as ready
Limb disorders v0.269 KIAA0586 Eleanor Williams Gene: kiaa0586 has been classified as Green List (High Evidence).
Limb disorders v0.269 KIAA0586 Eleanor Williams Classified gene: KIAA0586 as Green List (high evidence)
Limb disorders v0.269 KIAA0586 Eleanor Williams Added comment: Comment on list classification: Rated green because three different variants have been reported in individuals presenting with a polydactyly phenotype as part of Joubert syndrome or Short-rib thoracic dysplasia 14 with polydactyly. 1 variant is thought to be a founder mutation but functional studies support this being the causative mutation.
Limb disorders v0.269 KIAA0586 Eleanor Williams Gene: kiaa0586 has been classified as Green List (High Evidence).
Limb disorders v0.268 KIAA0586 Eleanor Williams Deleted their comment
Limb disorders v0.268 KIAA0586 Eleanor Williams Phenotypes for gene: KIAA0586 were changed from Short-rib thoracic dysplasia 14 with polydactyly 616546; Polydactyly to Short-rib thoracic dysplasia 14 with polydactyly 616546; Polydactyly; Joubert syndrome 23 616490
Limb disorders v0.267 KIAA0586 Eleanor Williams Publications for gene: KIAA0586 were set to 26166481; 26437029
Limb disorders v0.266 KIAA0586 Eleanor Williams Classified gene: KIAA0586 as Green List (high evidence)
Limb disorders v0.266 KIAA0586 Eleanor Williams Gene: kiaa0586 has been classified as Green List (High Evidence).
Limb disorders v0.265 KIAA0586 Eleanor Williams Classified gene: KIAA0586 as Amber List (moderate evidence)
Limb disorders v0.265 KIAA0586 Eleanor Williams Added comment: Comment on list classification: Rating green as three different variants have been reported in individuals presenting with a polydactyly phenotype as part of Joubert syndrome or Short-rib thoracic dysplasia 14 with polydactyly.
Limb disorders v0.265 KIAA0586 Eleanor Williams Gene: kiaa0586 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.264 KIAA0586 Eleanor Williams commented on gene: KIAA0586: Associated with Joubert syndrome 23 and Short-rib thoracic dysplasia 14 with polydactyly in OMIM and Joubert syndrome in Gene2Phenotype.

4 families described in PMID: 26166481 for Short-rib thoracic dysplasia 14 with polydactyly. One family is a consanguineous Lebanese family in which 2 fetuses exhibited severe hydrocephaly, polydactyly, and skeletal abnormalities. A homozygous nonsense mutation was identified (S77X). They identified 3 further unrelated Eastern European families with cerebral anomalies, polydactyly, and long-bone shortening, including short ribs, who were all homozygous for the same splice site variant in KIAA0586 (c.1815G-A). Haplotype analysis of these 3 families was consistent with a common ancestor, estimated to have lived 16 generations (480 years) earlier.

Bachmann-Gagescu et al. (2015) (PMID: 26096313) identified homozygous or compound heterozygous mutations in the KIAA0586 gene in individuals with Joubert syndrome-23 from 9 unrelated families. Only 1 patient of Middle easter origin had polydactyly (D566V variant).

In summary, three different variants have been reported in individuals presenting with a polydactyly phenotype as part of Joubert syndrome or Short-rib thoracic dysplasia 14 with polydactyly.
Limb disorders v0.264 PRMT7 Eleanor Williams Marked gene: PRMT7 as ready
Limb disorders v0.264 PRMT7 Eleanor Williams Gene: prmt7 has been classified as Green List (High Evidence).
Limb disorders v0.264 PRMT7 Eleanor Williams Classified gene: PRMT7 as Green List (high evidence)
Limb disorders v0.264 PRMT7 Eleanor Williams Added comment: Comment on list classification: Rated as Green as there are more than 3 cases of individuals with brachydactyly and LOF variants in the PRMT7 gene.
Limb disorders v0.264 PRMT7 Eleanor Williams Gene: prmt7 has been classified as Green List (High Evidence).
Limb disorders v0.263 PORCN Eleanor Williams Marked gene: PORCN as ready
Limb disorders v0.263 PORCN Eleanor Williams Gene: porcn has been classified as Green List (High Evidence).
Limb disorders v0.263 PORCN Eleanor Williams Classified gene: PORCN as Green List (high evidence)
Limb disorders v0.263 PORCN Eleanor Williams Added comment: Comment on list classification: Changing rating to Green. More than 3 cases where syndactyly is reported in patients with point mutations resulting in stop mutations in publication PMID:17546031 alone.
Limb disorders v0.263 PORCN Eleanor Williams Gene: porcn has been classified as Green List (High Evidence).
Limb disorders v0.262 DYNC2H1 Eleanor Williams Marked gene: DYNC2H1 as ready
Limb disorders v0.262 DYNC2H1 Eleanor Williams Gene: dync2h1 has been classified as Green List (High Evidence).
Limb disorders v0.262 DYNC2H1 Eleanor Williams Classified gene: DYNC2H1 as Green List (high evidence)
Limb disorders v0.262 DYNC2H1 Eleanor Williams Added comment: Comment on list classification: Promoting to green because there are more than 3 cases in which polydactyly/syndactyly are seen.
Limb disorders v0.262 DYNC2H1 Eleanor Williams Gene: dync2h1 has been classified as Green List (High Evidence).
Limb disorders v0.261 COL2A1 Eleanor Williams Marked gene: COL2A1 as ready
Limb disorders v0.261 COL2A1 Eleanor Williams Gene: col2a1 has been classified as Green List (High Evidence).
Limb disorders v0.261 NEK1 Eleanor Williams Marked gene: NEK1 as ready
Limb disorders v0.261 NEK1 Eleanor Williams Gene: nek1 has been classified as Green List (High Evidence).
Limb disorders v0.261 NEK1 Eleanor Williams Classified gene: NEK1 as Green List (high evidence)
Limb disorders v0.261 NEK1 Eleanor Williams Added comment: Comment on list classification: Rating this gene as green as there are > 3 cases where the patients show polydactyly/polysyndactyly.
Limb disorders v0.261 NEK1 Eleanor Williams Gene: nek1 has been classified as Green List (High Evidence).
Limb disorders v0.260 COL2A1 Eleanor Williams Publications for gene: COL2A1 were set to 14729840; 15266623
Limb disorders v0.259 COL2A1 Eleanor Williams Classified gene: COL2A1 as Green List (high evidence)
Limb disorders v0.259 COL2A1 Eleanor Williams Added comment: Comment on list classification: 3 patients with spondyloperipheral dysplasia and phenotypic features such as brachydactyly have been reported, with plausible disease causing mutations in COL2A1
Limb disorders v0.259 COL2A1 Eleanor Williams Gene: col2a1 has been classified as Green List (High Evidence).
Limb disorders v0.258 COL2A1 Eleanor Williams commented on gene: COL2A1: Associated with many conditions in OMIM including Spondyloperipheral dysplasia.

Zabel et al. (1996) (PMID: 8723097)  described a 5-bp duplication in exon 51 of the COL2A1 gene resulting in a frameshift in a patient with spondyloperipheral dysplasia. The patient’s phenotypes included Brachydactyly and short toes.

Zankl et al. (2004) (PMID: 15316962) identified heterozygous truncating mutations in the COL2A1 gene in two patients with a phenotype similar to that described by Zabel et al. (1996). Both developed brachydactyly type E like changes of fingers and toes in childhood. In both individuals, heterozygosity for novel, distinct mutations in COL2A1 were found.

Summary - 3 patients with spondyloperipheral dysplasia and phenotypic features such as brachydactyly have been reported, with plausible disease causing mutations in COL2A1.
Limb disorders v0.258 ORC1 Eleanor Williams Publications for gene: ORC1 were set to
Limb disorders v0.257 ORC1 Eleanor Williams commented on gene: ORC1: ORC1 is associated with Meier-Gorlin syndrome 1 in OMIM and Gene2Phenotype (confirmed).

> 3 cases of individuals with Meier-Goblin syndrome with short stature (dwarfism) are reported in  Bicknell et al. (2011)(PMID: 21358633),  Bicknell et al. (2011) (PMID: 21358632) and Guernsey et al. (2011) (PMID: 21358631). A variety of homozygous and compound heterozygous mutations in ORC1 were identified.
Limb disorders v0.257 CHSY1 Eleanor Williams Marked gene: CHSY1 as ready
Limb disorders v0.257 CHSY1 Eleanor Williams Gene: chsy1 has been classified as Green List (High Evidence).
Limb disorders v0.257 CHSY1 Eleanor Williams Classified gene: CHSY1 as Green List (high evidence)
Limb disorders v0.257 CHSY1 Eleanor Williams Added comment: Comment on list classification: Rating as green as there are > 3 cases of patients with a phenotype relevant to this panel with a plausible disease causing variant.
Limb disorders v0.257 CHSY1 Eleanor Williams Gene: chsy1 has been classified as Green List (High Evidence).
Limb disorders v0.256 CHSY1 Eleanor Williams commented on gene: CHSY1: Associated with Temtamy preaxial brachydactyly syndrome in OMIM and Gene2Phenotype.
Li et al (2010)(PMID: 21129728) describe 5 consanguineous TPBS families with several different homozygous variants in CHSY1. Patients from all families showed phenotypes relevant to this panel including syndactyly and preaxial brachydactyly.

Tian et al (2010)(PMID:  21129727) also describe a consanguineous family with two children showing preaxial brachydactyly among other features.

There are > 3 families/cases with patients showing relevant phenotypes and homozygous variants in CHSY1.
Limb disorders v0.256 SMO Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from 'Other' in order to capture variants within this gene in our current tiering pipeline.
Limb disorders v0.256 SMO Rebecca Foulger Mode of inheritance for gene: SMO was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.255 DDX59 Eleanor Williams Marked gene: DDX59 as ready
Limb disorders v0.255 DDX59 Eleanor Williams Gene: ddx59 has been classified as Green List (High Evidence).
Limb disorders v0.255 DDX59 Eleanor Williams Phenotypes for gene: DDX59 were changed from Polydactyly to Polydactyly; Orofaciodigital syndrome V 174300
Limb disorders v0.254 DDX59 Eleanor Williams Publications for gene: DDX59 were set to
Limb disorders v0.253 DDX59 Eleanor Williams Mode of inheritance for gene: DDX59 was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.252 DDX59 Eleanor Williams Classified gene: DDX59 as Green List (high evidence)
Limb disorders v0.252 DDX59 Eleanor Williams Added comment: Comment on list classification: > 3 families/cases with Orofaciodigital syndrome including polydactyly phenotype and a variant in this gene.
Limb disorders v0.252 DDX59 Eleanor Williams Gene: ddx59 has been classified as Green List (High Evidence).
Limb disorders v0.251 DDX59 Eleanor Williams commented on gene: DDX59
Limb disorders v0.249 RBM10 Eleanor Williams commented on gene: RBM10
Limb disorders v0.249 DVL2 Eleanor Williams Marked gene: DVL2 as ready
Limb disorders v0.249 DVL2 Eleanor Williams Gene: dvl2 has been classified as Red List (Low Evidence).
Limb disorders v0.249 DVL2 Eleanor Williams commented on gene: DVL2
Limb disorders v0.249 DLX6 Eleanor Williams commented on gene: DLX6
Limb disorders v0.249 POLL Sarah Leigh Marked gene: POLL as ready
Limb disorders v0.249 POLL Sarah Leigh Gene: poll has been classified as Red List (Low Evidence).
Limb disorders v0.249 PIK3CA Sarah Leigh Tag mosaicism tag was added to gene: PIK3CA.
Tag somatic tag was added to gene: PIK3CA.
Limb disorders v0.249 CKAP2L Eleanor Williams Marked gene: CKAP2L as ready
Limb disorders v0.249 CKAP2L Eleanor Williams Gene: ckap2l has been classified as Green List (High Evidence).
Limb disorders v0.249 IFT43 Eleanor Williams Marked gene: IFT43 as ready
Limb disorders v0.249 IFT43 Eleanor Williams Added comment: Comment when marking as ready: After review of literature, only 2 cases to date have been reported.
Limb disorders v0.249 IFT43 Eleanor Williams Gene: ift43 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.249 MIR17HG Sarah Leigh Marked gene: MIR17HG as ready
Limb disorders v0.249 MIR17HG Sarah Leigh Gene: mir17hg has been classified as Amber List (Moderate Evidence).
Limb disorders v0.249 IFT43 Eleanor Williams Classified gene: IFT43 as Amber List (moderate evidence)
Limb disorders v0.249 IFT43 Eleanor Williams Added comment: Comment on list classification: Only 2 cases/families to date
Limb disorders v0.249 IFT43 Eleanor Williams Gene: ift43 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.248 CKAP2L Eleanor Williams Phenotypes for gene: CKAP2L were changed from Polydactyly; Filippi syndrome 272440; FILIPPI SYNDROME. SYNDACTYLY, TYPE I, WITH MICROCEPHALY AND MENTAL RETARDATION to Polydactyly; Filippi syndrome 272440; FILIPPI SYNDROME. SYNDACTYLY, TYPE I, WITH MICROCEPHALY AND MENTAL RETARDATION
Limb disorders v0.248 CKAP2L Eleanor Williams Phenotypes for gene: CKAP2L were changed from Polydactyly to Polydactyly; Filippi syndrome 272440; FILIPPI SYNDROME. SYNDACTYLY, TYPE I, WITH MICROCEPHALY AND MENTAL RETARDATION
Limb disorders v0.248 CKAP2L Eleanor Williams Publications for gene: CKAP2L were set to
Limb disorders v0.248 CKAP2L Eleanor Williams Mode of inheritance for gene: CKAP2L was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.248 CKAP2L Eleanor Williams Classified gene: CKAP2L as Green List (high evidence)
Limb disorders v0.248 CKAP2L Eleanor Williams Added comment: Comment on list classification: Plausible disease causing variants in > 3 families.
Limb disorders v0.248 CKAP2L Eleanor Williams Gene: ckap2l has been classified as Green List (High Evidence).
Limb disorders v0.247 CKAP2L Eleanor Williams commented on gene: CKAP2L
Limb disorders v0.247 CCND2 Eleanor Williams Mode of inheritance for gene: CCND2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.246 CD96 Eleanor Williams Classified gene: CD96 as Red List (low evidence)
Limb disorders v0.246 CD96 Eleanor Williams Added comment: Comment on list classification: Leaving rating at red as only 1 reported case of a patient with limb abnormalities and a putative pathogenic variant in CD96
Limb disorders v0.246 CD96 Eleanor Williams Gene: cd96 has been classified as Red List (Low Evidence).
Limb disorders v0.246 CD96 Eleanor Williams Phenotypes for gene: CD96 were changed from Polydactyly to Polydactyly; C syndrome 211750
Limb disorders v0.246 CD96 Eleanor Williams Publications for gene: CD96 were set to
Limb disorders v0.245 CD96 Eleanor Williams Marked gene: CD96 as ready
Limb disorders v0.245 CD96 Eleanor Williams Added comment: Comment when marking as ready: Literature has been reviewed.
Limb disorders v0.245 CD96 Eleanor Williams Gene: cd96 has been classified as Red List (Low Evidence).
Limb disorders v0.245 CCND2 Eleanor Williams Marked gene: CCND2 as ready
Limb disorders v0.245 CCND2 Eleanor Williams Added comment: Comment when marking as ready: Rated green based on sufficient evidence.
Limb disorders v0.245 CCND2 Eleanor Williams Gene: ccnd2 has been classified as Green List (High Evidence).
Limb disorders v0.245 CD96 Eleanor Williams commented on gene: CD96
Limb disorders v0.245 CCND2 Eleanor Williams Publications for gene: CCND2 were set to
Limb disorders v0.244 CCND2 Eleanor Williams Phenotypes for gene: CCND2 were changed from Polydactyly to Polydactyly; Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 615938
Limb disorders v0.243 CCND2 Eleanor Williams Mode of inheritance for gene: CCND2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.243 CCND2 Eleanor Williams Classified gene: CCND2 as Green List (high evidence)
Limb disorders v0.243 CCND2 Eleanor Williams Added comment: Comment on list classification: More than 3 unrelated cases/families with plausible disease causing variants in this gene.
Limb disorders v0.243 CCND2 Eleanor Williams Gene: ccnd2 has been classified as Green List (High Evidence).
Limb disorders v0.242 CCND2 Eleanor Williams commented on gene: CCND2
Limb disorders v0.242 BTRC Eleanor Williams Marked gene: BTRC as ready
Limb disorders v0.242 BTRC Eleanor Williams Added comment: Comment when marking as ready: Review of literature in October 2018 - no new publications. So keeping rating as Amber.
Limb disorders v0.242 BTRC Eleanor Williams Gene: btrc has been classified as Amber List (Moderate Evidence).
Limb disorders v0.242 BMP4 Eleanor Williams Marked gene: BMP4 as ready
Limb disorders v0.242 BMP4 Eleanor Williams Added comment: Comment when marking as ready: rated green as 3 cases reported
Limb disorders v0.242 BMP4 Eleanor Williams Gene: bmp4 has been classified as Green List (High Evidence).
Limb disorders v0.242 BMP4 Eleanor Williams Phenotypes for gene: BMP4 were changed from Polydactyly to Polydactyly; Microphthalmia, syndromic 6 607932
Limb disorders v0.242 BMP4 Eleanor Williams Publications for gene: BMP4 were set to
Limb disorders v0.242 BMP4 Eleanor Williams Mode of inheritance for gene: BMP4 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.242 BMP4 Eleanor Williams Classified gene: BMP4 as Green List (high evidence)
Limb disorders v0.242 BMP4 Eleanor Williams Added comment: Comment on list classification: 3 cases with plausible disease causing variants in the gene have been reported.
Limb disorders v0.242 BMP4 Eleanor Williams Gene: bmp4 has been classified as Green List (High Evidence).
Limb disorders v0.241 BMP4 Eleanor Williams commented on gene: BMP4
Limb disorders v0.241 BBS1 Eleanor Williams Marked gene: BBS1 as ready
Limb disorders v0.241 BBS1 Eleanor Williams Added comment: Comment when marking as ready: Marked as read after reviewing available evidence
Limb disorders v0.241 BBS1 Eleanor Williams Gene: bbs1 has been classified as Green List (High Evidence).
Limb disorders v0.241 BBS1 Eleanor Williams commented on gene: BBS1: Note: is green on the Rare multisystem ciliopathy disorders panel.
Limb disorders v0.241 B9D2 Eleanor Williams Marked gene: B9D2 as ready
Limb disorders v0.241 B9D2 Eleanor Williams Added comment: Comment when marking as ready: Marked as ready after reviewing the available evidence
Limb disorders v0.241 B9D2 Eleanor Williams Gene: b9d2 has been classified as Red List (Low Evidence).
Limb disorders v0.241 B9D1 Eleanor Williams Marked gene: B9D1 as ready
Limb disorders v0.241 B9D1 Eleanor Williams Added comment: Comment when marking as ready: Marked as ready after reviewing evidence
Limb disorders v0.241 B9D1 Eleanor Williams Gene: b9d1 has been classified as Red List (Low Evidence).
Limb disorders v0.241 ARMC8 Eleanor Williams Marked gene: ARMC8 as ready
Limb disorders v0.241 ARMC8 Eleanor Williams Added comment: Comment when marking as ready: Rated based on search of literature and OMIM
Limb disorders v0.241 ARMC8 Eleanor Williams Gene: armc8 has been classified as Red List (Low Evidence).
Limb disorders v0.241 ARL6 Eleanor Williams Marked gene: ARL6 as ready
Limb disorders v0.241 ARL6 Eleanor Williams Added comment: Comment when marking as ready: Sufficient evidence to rate green.
Limb disorders v0.241 ARL6 Eleanor Williams Gene: arl6 has been classified as Green List (High Evidence).
Limb disorders v0.241 ARL6 Eleanor Williams commented on gene: ARL6: Note: also green on Rare multisystem ciliopathy disorders panel
Limb disorders v0.241 ALX3 Eleanor Williams Marked gene: ALX3 as ready
Limb disorders v0.241 ALX3 Eleanor Williams Added comment: Comment when marking as ready: Rated red after review of literature.
Limb disorders v0.241 ALX3 Eleanor Williams Gene: alx3 has been classified as Red List (Low Evidence).
Limb disorders v0.241 ALMS1 Eleanor Williams Marked gene: ALMS1 as ready
Limb disorders v0.241 ALMS1 Eleanor Williams Added comment: Comment when marking as ready: Rated red after review of literature
Limb disorders v0.241 ALMS1 Eleanor Williams Gene: alms1 has been classified as Red List (Low Evidence).
Limb disorders v0.241 ALMS1 Eleanor Williams Publications for gene: ALMS1 were set to
Limb disorders v0.240 AKT3 Eleanor Williams Marked gene: AKT3 as ready
Limb disorders v0.240 AKT3 Eleanor Williams Added comment: Comment when marking as ready: Rated red based on feedback from Genomics England Clinical Team
Limb disorders v0.240 AKT3 Eleanor Williams Gene: akt3 has been classified as Red List (Low Evidence).
Limb disorders v0.240 AKT3 Eleanor Williams Phenotypes for gene: AKT3 were changed from Polydactyly to Polydactyly; Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 615937
Limb disorders v0.239 AKT3 Eleanor Williams Publications for gene: AKT3 were set to
Limb disorders v0.238 AHI1 Eleanor Williams Marked gene: AHI1 as ready
Limb disorders v0.238 AHI1 Eleanor Williams Added comment: Comment when marking as ready: Rated as red based on feedback from Genomics England Clinical team
Limb disorders v0.238 AHI1 Eleanor Williams Gene: ahi1 has been classified as Red List (Low Evidence).
Limb disorders v0.238 AHI1 Eleanor Williams Phenotypes for gene: AHI1 were changed from Polydactyly to Polydactyly; Joubert syndrome 3 608629
Limb disorders v0.237 AHI1 Eleanor Williams Publications for gene: AHI1 were set to
Limb disorders v0.236 SMO Rebecca Foulger Classified gene: SMO as Green List (high evidence)
Limb disorders v0.236 SMO Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green: sufficient unrelated cases of syndactyly and/or preaxial polydactyly in Curry-Jones patients for inclusion on panel.
Limb disorders v0.236 SMO Rebecca Foulger Gene: smo has been classified as Green List (High Evidence).
Limb disorders v0.235 SMO Rebecca Foulger Added comment: Comment on mode of inheritance: Somatic mosaic.
Limb disorders v0.235 SMO Rebecca Foulger Mode of inheritance for gene: SMO was changed from to Other
Limb disorders v0.234 SMO Rebecca Foulger commented on gene: SMO: Added 'somatic' tag.
Limb disorders v0.234 SMO Rebecca Foulger Tag somatic tag was added to gene: SMO.
Limb disorders v0.234 TFAP2B Rebecca Foulger Marked gene: TFAP2B as ready
Limb disorders v0.234 TFAP2B Rebecca Foulger Gene: tfap2b has been classified as Green List (High Evidence).
Limb disorders v0.234 TFAP2B Rebecca Foulger Classified gene: TFAP2B as Green List (high evidence)
Limb disorders v0.234 TFAP2B Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green: Confirmed DD-G2P gene for Char syndrome, which includes hand anomalies. Although not all patients display a hand phenotype, there's sufficient cases for inclusion on the limb panel.
Limb disorders v0.234 TFAP2B Rebecca Foulger Gene: tfap2b has been classified as Green List (High Evidence).
Limb disorders v0.233 TFAP2B Rebecca Foulger commented on gene: TFAP2B: Confirmed DD-G2P gene for Char syndrome (MIM:169100). Char syndrome is characterized by the triad of patent ductus arteriosus (PDA), facial dysmorphism and hand anomalies including aplasia or hypoplasia of the middle phalanges of the fifth fingers or fifth finger clinodactyly. However, hand anomalies are not reported in all patients. Variants in TFAP2B can also cause PDA without facial dysmorphism or hand anomalies (MIM:617035).
Limb disorders v0.233 TFAP2B Rebecca Foulger Publications for gene: TFAP2B were set to 15684060; 11505339
Limb disorders v0.232 TFAP2B Rebecca Foulger commented on gene: TFAP2B: In a large 3-generation family segregating autosomal dominant Char syndrome (CHAR; 169100), Mani et al. (2005, 15684060) identified heterozygosity for a G-to-A transition at position +5 of the splice donor site of intron 3, a highly conserved nucleotide in the TFAP2B gene. Of the 22 affected members, all had clinodactyly. Chen et al (PMID:21643846) report the same variant in a Chinese family, but none of the affected individuals in the Chinese family exhibited the craniofacial or fifth-finger anomalies of Char syndrome.
Limb disorders v0.232 TFAP2B Rebecca Foulger commented on gene: TFAP2B
Limb disorders v0.232 TFAP2B Rebecca Foulger Phenotypes for gene: TFAP2B were changed from Polydactyly to Polydactyly; Clinodactyly; Char syndrome, 169100
Limb disorders v0.231 TFAP2B Rebecca Foulger Mode of inheritance for gene: TFAP2B was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.230 TFAP2B Rebecca Foulger Publications for gene: TFAP2B were set to
Limb disorders v0.229 ZIC3 Sarah Leigh gene: ZIC3 was added
gene: ZIC3 was added to Limb disorders. Sources: Expert Review Green
Mode of inheritance for gene: ZIC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZIC3 were set to 21465648; 20452998
Phenotypes for gene: ZIC3 were set to VACTERL association, X-linked 314390
Limb disorders v0.229 WNT7A Sarah Leigh Added phenotypes absence of a radius; Fuhrmann syndrome, 228930; Ulna and fibula, absence of, with severe limb deficiency, 276820; Short, bowed radii for gene: WNT7A
Limb disorders v0.229 UBE2T Sarah Leigh Source Expert Review Green was added to UBE2T.
Added phenotypes Fanconi Anemia, Complementation Group T, 616435 for gene: UBE2T
Limb disorders v0.229 TBX5 Sarah Leigh Mode of inheritance for gene TBX5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Holt-Oram syndrome,142900 for gene: TBX5
Publications for gene TBX5 were changed from to 8730285
Limb disorders v0.229 TBX3 Sarah Leigh Mode of inheritance for gene TBX3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Ulnar-mammary syndrome, 181450; Hypoplastic/absent/deformed radius for gene: TBX3
Limb disorders v0.229 SMC3 Sarah Leigh Mode of inheritance for gene SMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Cornelia de Lange syndrome 3, 610759 for gene: SMC3
Publications for gene SMC3 were changed from to 25125236
Limb disorders v0.229 SMC1A Sarah Leigh Added phenotypes Cornelia de Lange syndrome 2, 300590 for gene: SMC1A
Publications for gene SMC1A were changed from to 20358602
Limb disorders v0.229 SLX4 Sarah Leigh Source Expert Review Green was added to SLX4.
Mode of inheritance for gene SLX4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group P, 613951 for gene: SLX4
Publications for gene SLX4 were changed from to 21240277; 21240275
Limb disorders v0.229 SHOX Sarah Leigh Source Expert Review Green was added to SHOX.
Added phenotypes Langer mesomelic dysplasia, 249700; dorsolateral bowed, short radii; bowing of the radius; curved radius; radioulnar shortening; Leri-Weill dyschondrosteosis, 127300 for gene: SHOX
Limb disorders v0.229 SF3B4 Sarah Leigh Mode of inheritance for gene SF3B4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Acrofacial dysostosis 1, Nager type, 154400 for gene: SF3B4
Limb disorders v0.229 SALL4 Sarah Leigh Added phenotypes Duane-radial ray syndrome, 607323; IVIC syndrome, 147750 for gene: SALL4
Limb disorders v0.229 SALL1 Sarah Leigh Mode of inheritance for gene SALL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Townes Brocks syndrome (Renal-Ear-Anal-Radial syndrome), 107480 for gene: SALL1
Limb disorders v0.229 RPS7 Sarah Leigh Source Expert Review Green was added to RPS7.
Mode of inheritance for gene RPS7 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Diamond-Blackfan anemia 8, 612563; upper limb malformation for gene: RPS7
Publications for gene RPS7 were changed from to 19061985
Limb disorders v0.229 RPS26 Sarah Leigh Source Expert Review Green was added to RPS26.
Mode of inheritance for gene RPS26 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Diamond-Blackfan anemia 10, 613309; upper limb malformation for gene: RPS26
Publications for gene RPS26 were changed from to 20116044
Limb disorders v0.229 RPS24 Sarah Leigh Source Expert Review Green was added to RPS24.
Mode of inheritance for gene RPS24 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Diamond-Blackfan anemia 3, 610629; upper limb malformation for gene: RPS24
Publications for gene RPS24 were changed from to 17186470; 2210388; 8647458; 19689926; 19773262
Limb disorders v0.229 RPS19 Sarah Leigh Source Expert Review Green was added to RPS19.
Mode of inheritance for gene RPS19 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Diamond-Blackfan anemia 1, 105650; Triphalangeal thumbs; Hypoplastic thumbs; Mild radial hypoplasia; Absent thumbs for gene: RPS19
Publications for gene RPS19 were changed from to 15384984; 9988267; 1746615
Limb disorders v0.229 RPS17 Sarah Leigh Source Expert Review Green was added to RPS17.
Mode of inheritance for gene RPS17 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Diamond-Blackfan anemia 4, 612527 for gene: RPS17
Publications for gene RPS17 were changed from to 17647292; 19953637; 22045982; 19061985
Limb disorders v0.229 RPS10 Sarah Leigh Source Expert Review Green was added to RPS10.
Mode of inheritance for gene RPS10 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Diamond-Blackfan anemia 9, 613308; upper limb malformation for gene: RPS10
Publications for gene RPS10 were changed from to 20116044
Limb disorders v0.229 RPL5 Sarah Leigh Source Expert Review Green was added to RPL5.
Mode of inheritance for gene RPL5 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Diamond-Blackfan anemia 6, 612561; thumb abnormalities for gene: RPL5
Publications for gene RPL5 were changed from to 19191325; 19061985
Limb disorders v0.229 RPL35A Sarah Leigh Source Expert Review Green was added to RPL35A.
Mode of inheritance for gene RPL35A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Diamond-Blackfan anemia 5, 612528; upper limb malformation for gene: RPL35A
Publications for gene RPL35A were changed from to 18535205
Limb disorders v0.229 RPL11 Sarah Leigh Source Expert Review Green was added to RPL11.
Mode of inheritance for gene RPL11 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Diamond-Blackfan anemia 7, 612562; hypoplastic thumb; thumb abnormalities for gene: RPL11
Publications for gene RPL11 were changed from to 19191325; 19061985
Limb disorders v0.229 RECQL4 Sarah Leigh Added phenotypes Rothmund-Thomson syndrome, 268400; RAPILINO syndrome, 266280; Baller-Gerold syndrome, 218600 for gene: RECQL4
Limb disorders v0.229 RBM8A Sarah Leigh Added phenotypes Thrombocytopenia-absent radius syndrome, 274000 for gene: RBM8A
Publications for gene RBM8A were changed from to 22366785
Limb disorders v0.229 PALB2 Sarah Leigh Source Expert Review Green was added to PALB2.
Mode of inheritance for gene PALB2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group N, 610832 for gene: PALB2
Publications for gene PALB2 were changed from to 17200671; 17200672
Limb disorders v0.229 NIPBL Sarah Leigh Mode of inheritance for gene NIPBL was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes CDLS1; Cornelia de Lange syndrome 1, 122470; Dislocation of the radial head; upper limb anomalies for gene: NIPBL
Limb disorders v0.229 LMBR1 Sarah Leigh Mode of inheritance for gene LMBR1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Triphalangeal Thumb-Polysyndactyly Syndrome; Laurin-Sandrow syndrome,135750; Triphalangeal thumb type I,174500 for gene: LMBR1
Limb disorders v0.229 KCNH1 Sarah Leigh Source Expert Review Green was added to KCNH1.
Added phenotypes Hypoplasia of terminal phalanges; Temple-Baraitser syndrome, 611816 for gene: KCNH1
Limb disorders v0.229 HOXA13 Sarah Leigh Added phenotypes Hand-foot-uterus syndrome, 140000 for gene: HOXA13
Publications for gene HOXA13 were changed from to 10839976; 9020844
Limb disorders v0.229 HDAC8 Sarah Leigh Source Expert Review Green was added to HDAC8.
Added phenotypes Cornelia de Lange syndrome 5, 300882 for gene: HDAC8
Limb disorders v0.229 FLNA Sarah Leigh Added phenotypes Melnick-Needles syndrome, 309350 for gene: FLNA
Publications for gene FLNA were changed from to 12612583
Limb disorders v0.229 FIG4 Sarah Leigh Source Expert Review Green was added to FIG4.
Added phenotypes Aplastic/hypoplastic thumbs; Yunis-Varon syndrome, 216340; absent thumbs for gene: FIG4
Publications for gene FIG4 were changed from to 23623387
Limb disorders v0.229 FGFR3 Sarah Leigh Mode of inheritance for gene FGFR3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes short radius; LADD syndrome, 149730; Limb defects most often involved the thumbs, ranging from total aplasia to hypoplastic, digitalized, triphalangeal, and duplicated thumbs for gene: FGFR3
Limb disorders v0.229 FGFR2 Sarah Leigh Mode of inheritance for gene FGFR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes short radius; LADD syndrome, 149730; Limb defects most often involved the thumbs, ranging from total aplasia to hypoplastic, digitalized, triphalangeal, and duplicated thumbs for gene: FGFR2
Limb disorders v0.229 FGF10 Sarah Leigh Mode of inheritance for gene FGF10 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes short radius; LADD syndrome, 149730; Limb defects most often involved the thumbs, ranging from total aplasia to hypoplastic, digitalized, triphalangeal, and duplicated thumbs for gene: FGF10
Limb disorders v0.229 FANCL Sarah Leigh Source Expert Review Green was added to FANCL.
Mode of inheritance for gene FANCL was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group L, 614083 for gene: FANCL
Publications for gene FANCL were changed from to 25754594; 12973351; 19405097; 12724401
Limb disorders v0.229 FANCI Sarah Leigh Source Expert Review Green was added to FANCI.
Mode of inheritance for gene FANCI was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group I, 609053 for gene: FANCI
Publications for gene FANCI were changed from to 11239453; 17452773
Limb disorders v0.229 FANCG Sarah Leigh Source Expert Review Green was added to FANCG.
Mode of inheritance for gene FANCG was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group G, 614082 for gene: FANCG
Publications for gene FANCG were changed from to 9806548
Limb disorders v0.229 FANCF Sarah Leigh Source Expert Review Green was added to FANCF.
Mode of inheritance for gene FANCF was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group F, 603467 for gene: FANCF
Publications for gene FANCF were changed from to 10615118
Limb disorders v0.229 FANCE Sarah Leigh Source Expert Review Green was added to FANCE.
Mode of inheritance for gene FANCE was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group E, 600901 for gene: FANCE
Publications for gene FANCE were changed from to 9147877; 10205272; 7662964; 9382107
Limb disorders v0.229 FANCD2 Sarah Leigh Source Expert Review Green was added to FANCD2.
Mode of inheritance for gene FANCD2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group D2, 227646 for gene: FANCD2
Publications for gene FANCD2 were changed from to 11239454
Limb disorders v0.229 FANCC Sarah Leigh Source Expert Review Green was added to FANCC.
Mode of inheritance for gene FANCC was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group C, 227645 for gene: FANCC
Publications for gene FANCC were changed from to 1574115
Limb disorders v0.229 FANCB Sarah Leigh Source Expert Review Green was added to FANCB.
Mode of inheritance for gene FANCB was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Added phenotypes Fanconi anemia, complementation group B, 300514; VACTERL Association with Hydrocephalus; Vacterl Association, X-Linked, With Or Without Hydrocephalus; Fanconi Anemia, Complementation Group B; VACTERL-Hydrocephalus Syndrome; Fanconi Anemia, X-Linked; Fanconi Anemia Type B for gene: FANCB
Publications for gene FANCB were changed from to 15502827
Limb disorders v0.229 FANCA Sarah Leigh Source Expert Review Green was added to FANCA.
Mode of inheritance for gene FANCA was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group A, 227650 for gene: FANCA
Publications for gene FANCA were changed from to 8896563
Limb disorders v0.229 ESCO2 Sarah Leigh Source Expert Review Green was added to ESCO2.
Added phenotypes absence of radii, SC phocomelia syndrome, 269000; Roberts syndrome, 268300; radial aplasia for gene: ESCO2
Limb disorders v0.229 ERCC4 Sarah Leigh Source Expert Review Green was added to ERCC4.
Mode of inheritance for gene ERCC4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group Q, 615272 for gene: ERCC4
Publications for gene ERCC4 were changed from to 23623389; 23623386; 24027083
Limb disorders v0.229 BRIP1 Sarah Leigh Source Expert Review Green was added to BRIP1.
Mode of inheritance for gene BRIP1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group J, 609054 for gene: BRIP1
Publications for gene BRIP1 were changed from to 16153896; 16116424; 14630800; 16116423
Limb disorders v0.229 BRCA2 Sarah Leigh Source Expert Review Green was added to BRCA2.
Mode of inheritance for gene BRCA2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group D1, 605724 for gene: BRCA2
Publications for gene BRCA2 were changed from to 11239453; 12065746; 14670928; 28185119
Limb disorders v0.228 UBE2T Sarah Leigh gene: UBE2T was added
gene: UBE2T was added to Limb disorders. Sources: Other
Mode of inheritance for gene: UBE2T was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE2T were set to 26046368; 26119737; 26085575
Phenotypes for gene: UBE2T were set to Fanconi Anemia, Complementation Group T, 616435
Limb disorders v0.228 SHOX Sarah Leigh gene: SHOX was added
gene: SHOX was added to Limb disorders. Sources: Other
Mode of inheritance for gene: SHOX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SHOX were set to Langer mesomelic dysplasia, 249700; radioulnar shortening; bowing of the radius; Leri-Weill dyschondrosteosis, 127300
Limb disorders v0.228 KCNH1 Sarah Leigh gene: KCNH1 was added
gene: KCNH1 was added to Limb disorders. Sources: Other
Mode of inheritance for gene: KCNH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNH1 were set to 25420144
Phenotypes for gene: KCNH1 were set to Temple-Baraitser syndrome, 611816
Limb disorders v0.228 HDAC8 Sarah Leigh gene: HDAC8 was added
gene: HDAC8 was added to Limb disorders. Sources: Other
Mode of inheritance for gene: HDAC8 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: HDAC8 were set to Cornelia de Lange syndrome 5, 300882
Limb disorders v0.228 FIG4 Sarah Leigh gene: FIG4 was added
gene: FIG4 was added to Limb disorders. Sources: Other
Mode of inheritance for gene: FIG4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FIG4 were set to Yunis-Varon syndrome, 216340
Limb disorders v0.228 ESCO2 Sarah Leigh gene: ESCO2 was added
gene: ESCO2 was added to Limb disorders. Sources: Other
Mode of inheritance for gene: ESCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ESCO2 were set to absence of radii, SC phocomelia syndrome, 269000; Roberts syndrome, 268300; radial aplasia
Limb disorders v0.227 TFAP2A Rebecca Foulger Marked gene: TFAP2A as ready
Limb disorders v0.227 TFAP2A Rebecca Foulger Added comment: Comment when marking as ready: Amber rating while awaiting further dactyly cases.
Limb disorders v0.227 TFAP2A Rebecca Foulger Gene: tfap2a has been classified as Amber List (Moderate Evidence).
Limb disorders v0.227 TFAP2A Rebecca Foulger commented on gene: TFAP2A: Added 'watchlist' tag while awaiting further cases.
Limb disorders v0.227 TFAP2A Rebecca Foulger Tag watchlist tag was added to gene: TFAP2A.
Limb disorders v0.227 TFAP2A Rebecca Foulger Classified gene: TFAP2A as Amber List (moderate evidence)
Limb disorders v0.227 TFAP2A Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber: Confirmed DD-G2P gene for Branchiooculofacial syndrome (MIM:113620) which can present with Polydactyly and Clinodactyly. Currently insufficient cases of dactyly phenotypes for diagnostic rating (PMIDs:20358615, 19685247).
Limb disorders v0.227 TFAP2A Rebecca Foulger Gene: tfap2a has been classified as Amber List (Moderate Evidence).
Limb disorders v0.226 TFAP2A Rebecca Foulger commented on gene: TFAP2A: Added 'deletions' tag based on Syndactyly patients in PMID:19685247 with whole gene deletions.
Limb disorders v0.226 TFAP2A Rebecca Foulger Tag deletions tag was added to gene: TFAP2A.
Limb disorders v0.226 TFAP2A Rebecca Foulger commented on gene: TFAP2A: Gestri et al 2009 (PMID:19685247) analyzed the TFAP2A gene in 37 patients with developmental eye defects plus variable defects associated with BOFS. A 5 year old boy with 5th finger clinodactyly (amongst other phenotypes) had a 12bp deletion resulting in the deletion of 4 amino acids (Glu233 to Arg236) in TFAP2A. Whole gene deletion was seen in a further 3 patients which all presented with Syndactyly.
Limb disorders v0.226 TFAP2A Rebecca Foulger commented on gene: TFAP2A: 1 BOFS patient was reported in Reiber et al 2010 (PMID:20358615) with severe Syndactyly and a c.806T>C (p.Leu269Pro) de novo missense variant in TFAP2A.
Limb disorders v0.226 TFAP2A Rebecca Foulger Publications for gene: TFAP2A were set to
Limb disorders v0.225 TFAP2A Rebecca Foulger Phenotypes for gene: TFAP2A were changed from Polydactyly to Polydactyly; Branchiooculofacial syndrome, 113620; Clinodactyly; Syndactyly
Limb disorders v0.224 TFAP2A Rebecca Foulger Added comment: Comment on mode of inheritance: Monoallelic MOI supported by OMIM and DD-G2P.
Limb disorders v0.224 TFAP2A Rebecca Foulger Mode of inheritance for gene: TFAP2A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.223 TCTN3 Rebecca Foulger Publications for gene: TCTN3 were set to
Limb disorders v0.222 TCTN3 Rebecca Foulger Marked gene: TCTN3 as ready
Limb disorders v0.222 TCTN3 Rebecca Foulger Added comment: Comment when marking as ready: Sufficient cases (>3) of polydactyly in patients with TCTN3 homozyous/compound het variants.
Limb disorders v0.222 TCTN3 Rebecca Foulger Gene: tctn3 has been classified as Green List (High Evidence).
Limb disorders v0.222 TCTN3 Rebecca Foulger Classified gene: TCTN3 as Green List (high evidence)
Limb disorders v0.222 TCTN3 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green: Confirmed DD-G2P gene for Orofaciodigital syndrome IV, 258860 (Mohr-Majewski syndrome) which can present with Polydactyly, Brachydactyly, Clinodactyly or Syndactyly. >3 polydactyly cases from multiple populations reported in consanguineous families in PMID:22883145. Multiple variants identified in this paper (homozgyous or compound heterozygous).
Limb disorders v0.222 TCTN3 Rebecca Foulger Gene: tctn3 has been classified as Green List (High Evidence).
Limb disorders v0.221 TCTN3 Rebecca Foulger commented on gene: TCTN3: Thomas et al. 2012 (PMID:22883145) identified a nonsensense variant in TCTN3 in an aborted fetus born to a consanguineous Senegal family. Amongst other features, the fetus had polydactyly of four limbs and bowing of long bones with severe tibia hypoplasia. They identified 2 additional homozygous variants in three other fetuses (from Pakistan and Tunisia), all of whom displayed polydactyly (Table 1) together with bone defects including femoral bowing and club foot. They also reported compound heterozygous variants in 2 French fetal siblings with Orofaciodigital syndrome IV, 258860 including polydactyly. Additionally they report 2 Turkish siblings with Joubert syndrome (MIM:614815) and homozygous TCTN3 variants; one was reported with polydactyly.
Limb disorders v0.221 TCTN3 Rebecca Foulger Phenotypes for gene: TCTN3 were changed from Polydactyly to Polydactyly; Joubert syndrome 18, 614815; Orofaciodigital syndrome IV, 258860
Limb disorders v0.220 TCTN3 Rebecca Foulger Added comment: Comment on mode of inheritance: Biallelic MOI supported by OMIM and Gene2Phenotype.
Limb disorders v0.220 TCTN3 Rebecca Foulger Mode of inheritance for gene: TCTN3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.219 TCTEX1D2 Rebecca Foulger Mode of inheritance for gene: TCTEX1D2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.218 TCTN2 Rebecca Foulger Added comment: Comment on mode of inheritance: Biallelic MOI confirmed by OMIM and Gene2Phenotype.
Limb disorders v0.218 TCTN2 Rebecca Foulger Mode of inheritance for gene: TCTN2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.217 TCTN2 Rebecca Foulger Marked gene: TCTN2 as ready
Limb disorders v0.217 TCTN2 Rebecca Foulger Added comment: Comment when marking as ready: 2 cases of polydactyl in literature plus mouse model.
Limb disorders v0.217 TCTN2 Rebecca Foulger Gene: tctn2 has been classified as Green List (High Evidence).
Limb disorders v0.217 TCTN2 Rebecca Foulger Classified gene: TCTN2 as Green List (high evidence)
Limb disorders v0.217 TCTN2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green: 2 cases of polydactyly in literature as part of Joubert syndrome (PMID:25118024) and Meckel-Gruber syndrome (PMID:21462283) PLUS mouse model of polydactyly (PMID:21565611).
Limb disorders v0.217 TCTN2 Rebecca Foulger Gene: tctn2 has been classified as Green List (High Evidence).
Limb disorders v0.216 TCTN2 Rebecca Foulger Phenotypes for gene: TCTN2 were changed from Polydactyly; Joubert syndrome 24, 616654, ?Meckel syndrome 8, 613885; postaxial polydactyly to Polydactyly; Joubert syndrome 24, 616654; ?Meckel syndrome 8, 613885; postaxial polydactyly
Limb disorders v0.215 TCTN2 Rebecca Foulger commented on gene: TCTN2: Sang et al (2011, PMID:21565611) report a mouse model of Tctn2-/- embryos that exhibit defects including single hindlimb preaxial polydactyly, either bilaterally or unilaterally.
Limb disorders v0.215 TCTN2 Rebecca Foulger Publications for gene: TCTN2 were set to 25118024; 21565611
Limb disorders v0.214 TCTN2 Rebecca Foulger commented on gene: TCTN2: In affected members of a consanguineous Arab family with Meckel-Gruber syndrome, Shaheen et al. (2011, PMID:21462283) identified homozygosity for a splice site mutation in the TCTN2 gene (1506-2A-G). Phenotypes included polydactyly in all recorded patients.
Limb disorders v0.214 TCTN2 Rebecca Foulger Publications for gene: TCTN2 were set to
Limb disorders v0.213 TCTN2 Rebecca Foulger commented on gene: TCTN2: Huppke et al. (2015, PMID:25118024) reported a 7.5-year-old Turkish boy, born of consanguineous parents, with a neurodevelopmental disorder consistent with Joubert syndrome. At birth, the patient was noted to have postaxial hexadactyly of all 4 extremities. The authors identified a homozygous splice site mutation in the TCTN2 gene (c.1235-1G-A, NM_024809.4). The unaffected mother was heterozygous for the variant.
Limb disorders v0.213 TCTN2 Rebecca Foulger commented on gene: TCTN2
Limb disorders v0.213 TCTN2 Rebecca Foulger Phenotypes for gene: TCTN2 were changed from Polydactyly to Polydactyly; Joubert syndrome 24, 616654, ?Meckel syndrome 8, 613885; postaxial polydactyly
Limb disorders v0.212 DYNC2H1 Rebecca Foulger commented on gene: DYNC2H1
Limb disorders v0.212 DYNC2H1 Rebecca Foulger Publications for gene: DYNC2H1 were set to 19442771; 19361615; 22499340
Limb disorders v0.211 TCTEX1D2 Rebecca Foulger Marked gene: TCTEX1D2 as ready
Limb disorders v0.211 TCTEX1D2 Rebecca Foulger Gene: tctex1d2 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.211 TCTEX1D2 Rebecca Foulger commented on gene: TCTEX1D2: Added 'watchlist' tag.
Limb disorders v0.211 TCTEX1D2 Rebecca Foulger Tag watchlist tag was added to gene: TCTEX1D2.
Limb disorders v0.211 TCTEX1D2 Rebecca Foulger Classified gene: TCTEX1D2 as Amber List (moderate evidence)
Limb disorders v0.211 TCTEX1D2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber: Two cases (PMID:26044572) presenting with polydactyly and/or brachydactyly as part of Short-rib thoracic dysplasia. A further case in the same paper removes part of the TM4SF19 gene in addition to part of the TCTEX1D2 gene. Therefore require further evidence of TCTEX1D2 variants causing limb phenotype before rating Green.
Limb disorders v0.211 TCTEX1D2 Rebecca Foulger Gene: tctex1d2 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.210 TCTEX1D2 Rebecca Foulger commented on gene: TCTEX1D2: In a third family (UCL4) reported by Schmidts et al. (2015, PMID:26044572), 3 affected sibs were homozygous for a more than 10-kb deletion removing the start codon and exons 1 and 2 of the TCTEX1D2 gene (and exons 2-5 of the neighbouring TM4SF19 gene). The deletion was also detected in 2 apparently unaffected sibs, indicating reduced penetrance. Some members of this family showed mild brachydactyly.
Limb disorders v0.210 TCTEX1D2 Rebecca Foulger commented on gene: TCTEX1D2
Limb disorders v0.210 TCTEX1D2 Rebecca Foulger Publications for gene: TCTEX1D2 were set to
Limb disorders v0.209 TCTEX1D2 Rebecca Foulger Phenotypes for gene: TCTEX1D2 were changed from Polydactyly to Polydactyly; Short-rib thoracic dysplasia 17 with or without polydactyly, 617405; Brachydactyly
Limb disorders v0.208 TBX22 Rebecca Foulger Marked gene: TBX22 as ready
Limb disorders v0.208 TBX22 Rebecca Foulger Gene: tbx22 has been classified as Red List (Low Evidence).
Limb disorders v0.208 TBX22 Rebecca Foulger Publications for gene: TBX22 were set to 21375406; 839509
Limb disorders v0.207 TBX22 Rebecca Foulger Classified gene: TBX22 as Red List (low evidence)
Limb disorders v0.207 TBX22 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Red: there is some evidence linking limb anomalies to TBX22 variants (PMID:21375406) but currently insufficient cases for inclusion on a diagnostic panel.
Limb disorders v0.207 TBX22 Rebecca Foulger Gene: tbx22 has been classified as Red List (Low Evidence).
Limb disorders v0.206 TBX22 Rebecca Foulger commented on gene: TBX22: Abruzzo-Erickson syndrome (MIM:302905, reported by Abruzzo and Erickson in 1977, PMID:839509) includes radial synostosis (an abnormal connection (synostosis) of the radius and ulna (bones in the forearm) at birth).
Limb disorders v0.206 TBX22 Rebecca Foulger Publications for gene: TBX22 were set to
Limb disorders v0.205 TBX22 Rebecca Foulger commented on gene: TBX22
Limb disorders v0.205 TBX22 Rebecca Foulger Phenotypes for gene: TBX22 were changed from Polydactyly; ?Abruzzo-Erickson syndrome, 302905; Cleft palate with ankyloglossia, 303400; Radioulnar synostosis to Polydactyly; ?Abruzzo-Erickson syndrome, 302905; Cleft palate with ankyloglossia, 303400; Radioulnar synostosis; upper limb anomalies; clinodactyly
Limb disorders v0.204 TBX22 Rebecca Foulger Phenotypes for gene: TBX22 were changed from Polydactyly to Polydactyly; ?Abruzzo-Erickson syndrome, 302905; Cleft palate with ankyloglossia, 303400; Radioulnar synostosis
Limb disorders v0.203 TBX22 Rebecca Foulger Mode of inheritance for gene: TBX22 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Limb disorders v0.202 SPINT2 Rebecca Foulger Marked gene: SPINT2 as ready
Limb disorders v0.202 SPINT2 Rebecca Foulger Gene: spint2 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.202 SPINT2 Rebecca Foulger commented on gene: SPINT2: Added 'watchlist' tag: require further evidence for a diagnostic rating.
Limb disorders v0.202 SPINT2 Rebecca Foulger Tag watchlist tag was added to gene: SPINT2.
Limb disorders v0.202 SPINT2 Rebecca Foulger Classified gene: SPINT2 as Amber List (moderate evidence)
Limb disorders v0.202 SPINT2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber. 2 cases from literature where congenital diarrhea (CSD) presents with hexadactyly. Need more evidence before rating as diagnostic.
Limb disorders v0.202 SPINT2 Rebecca Foulger Gene: spint2 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.201 SEM1 Louise Daugherty Added comment: Comment on mode of inheritance: added MOI suggested by expert review
Limb disorders v0.201 SEM1 Louise Daugherty Mode of inheritance for gene: SEM1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.200 SPINT2 Rebecca Foulger Publications for gene: SPINT2 were set to 24142340; 19185281
Limb disorders v0.199 SPINT2 Rebecca Foulger Phenotypes for gene: SPINT2 were changed from Polydactyly; Diarrhea 3, secretory sodium, congenital, syndromic, 270420; hexadactyly to Polydactyly; Diarrhea 3, secretory sodium, congenital, syndromic, 270420; hexadactyly; congenital sodium diarrhea with additional syndromic features
Limb disorders v0.198 ARL6 Eleanor Williams Phenotypes for gene: ARL6 were changed from Polydactyly to Polydactyly; Bardet-Biedl syndrome 3 600151
Limb disorders v0.197 ARL6 Eleanor Williams Publications for gene: ARL6 were set to
Limb disorders v0.196 ARL6 Eleanor Williams Mode of inheritance for gene: ARL6 was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.195 ARL6 Eleanor Williams Classified gene: ARL6 as Green List (high evidence)
Limb disorders v0.195 ARL6 Eleanor Williams Added comment: Comment on list classification: Rated green as variants in the ARL6 gene is associated with Bardet-Biedl syndrome 3 in more than cases/families.
Limb disorders v0.195 ARL6 Eleanor Williams Gene: arl6 has been classified as Green List (High Evidence).
Limb disorders v0.194 BBS1 Eleanor Williams Phenotypes for gene: BBS1 were changed from Polydactyly to Polydactyly; Bardet-Biedl syndrome 1209900
Limb disorders v0.193 BBS1 Eleanor Williams Publications for gene: BBS1 were set to
Limb disorders v0.192 BBS1 Eleanor Williams Added comment: Comment on mode of inheritance: Also reported as Digenic recessive in OMIM
Limb disorders v0.192 BBS1 Eleanor Williams Mode of inheritance for gene: BBS1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.191 BBS1 Eleanor Williams Classified gene: BBS1 as Green List (high evidence)
Limb disorders v0.191 BBS1 Eleanor Williams Added comment: Comment on list classification: More than 3 cases/families reported of variants in this gene in individuals with Bardet-Biedl syndrome 1.
Limb disorders v0.191 BBS1 Eleanor Williams Gene: bbs1 has been classified as Green List (High Evidence).
Limb disorders v0.190 BBS1 Eleanor Williams commented on gene: BBS1
Limb disorders v0.190 B9D2 Eleanor Williams Classified gene: B9D2 as Red List (low evidence)
Limb disorders v0.190 B9D2 Eleanor Williams Added comment: Comment on list classification: Rating as red as only 1 variant reported in 1 family in association with Meckel syndrome 10.
Limb disorders v0.190 B9D2 Eleanor Williams Gene: b9d2 has been classified as Red List (Low Evidence).
Limb disorders v0.189 B9D2 Eleanor Williams Phenotypes for gene: B9D2 were changed from Polydactyly to Polydactyly; ?Meckel syndrome 10 614175; Joubert syndrome 34 614175
Limb disorders v0.188 B9D2 Eleanor Williams Publications for gene: B9D2 were set to
Limb disorders v0.187 B9D2 Eleanor Williams commented on gene: B9D2
Limb disorders v0.187 B9D1 Eleanor Williams Phenotypes for gene: B9D1 were changed from Polydactyly to Polydactyly; ?Meckel syndrome 9 614209; Joubert syndrome 27 617120
Limb disorders v0.186 B9D1 Eleanor Williams Publications for gene: B9D1 were set to
Limb disorders v0.185 B9D1 Eleanor Williams Classified gene: B9D1 as Red List (low evidence)
Limb disorders v0.185 B9D1 Eleanor Williams Added comment: Comment on list classification: Rating red as insufficient evidence to associate this gene with Meckel syndrome 9.
Limb disorders v0.185 B9D1 Eleanor Williams Gene: b9d1 has been classified as Red List (Low Evidence).
Limb disorders v0.184 B9D1 Eleanor Williams commented on gene: B9D1
Limb disorders v0.184 ARMC8 Eleanor Williams Classified gene: ARMC8 as Red List (low evidence)
Limb disorders v0.184 ARMC8 Eleanor Williams Added comment: Comment on list classification: No evidence found for an association of this gene with any limb disorder phenotypes.
Limb disorders v0.184 ARMC8 Eleanor Williams Gene: armc8 has been classified as Red List (Low Evidence).
Limb disorders v0.183 ARMC8 Eleanor Williams commented on gene: ARMC8
Limb disorders v0.183 ARL6 Eleanor Williams commented on gene: ARL6
Limb disorders v0.183 ALX3 Eleanor Williams Classified gene: ALX3 as Red List (low evidence)
Limb disorders v0.183 ALX3 Eleanor Williams Added comment: Comment on list classification: Rating this gene as red as no clear evidence that ALX3 is associated with a limb disorder phenotype.
Limb disorders v0.183 ALX3 Eleanor Williams Gene: alx3 has been classified as Red List (Low Evidence).
Limb disorders v0.182 ALX3 Eleanor Williams commented on gene: ALX3
Limb disorders v0.182 AKT3 Eleanor Williams Classified gene: AKT3 as Red List (low evidence)
Limb disorders v0.182 AKT3 Eleanor Williams Added comment: Comment on list classification: Rating as red. Insufficient evidence for AKT3 association with polydactyly.
Limb disorders v0.182 AKT3 Eleanor Williams Gene: akt3 has been classified as Red List (Low Evidence).
Limb disorders v0.181 AHI1 Eleanor Williams Classified gene: AHI1 as Red List (low evidence)
Limb disorders v0.181 AHI1 Eleanor Williams Added comment: Comment on list classification: Rating as red from feedback from Genomics England clinical team. The presentation of Joubert syndrome is usually broader than isolated polydactyly. It could be useful for the diagnosis of neonates but not for any patients older than this.
Limb disorders v0.181 AHI1 Eleanor Williams Gene: ahi1 has been classified as Red List (Low Evidence).
Limb disorders v0.180 SPINT2 Rebecca Foulger commented on gene: SPINT2: PMID:19185281 (Heinz-Erian et al., 2009) reviewed data from a large cohort of CSD patients (n = 24).1 Swedish female patient with syndromic CSD had a homozygous SPINT2 allele (c.488A→G, p.Y163C) and presented with an extra digit on her right hand.
Limb disorders v0.180 SPINT2 Rebecca Foulger commented on gene: SPINT2: In 9 children from 7 families with MIM:270420, Salomon et al. (2014, PMID:24142340) identified either homozygosity for the Y163C mutation in SPINT2 or compound heterozygosity for Y163C and another variant in SPINT2. One of the patients (an Italian boy) exhibited additional hexadactyly.
Limb disorders v0.180 SPINT2 Rebecca Foulger Added comment: Comment on phenotypes: Biallelic, loss of function mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea (CSD) which can (rarely) include hexadactyly.
Limb disorders v0.180 SPINT2 Rebecca Foulger Phenotypes for gene: SPINT2 were changed from Polydactyly; Diarrhea 3, secretory sodium, congenital, syndromic, 270420; hexadactyly to Polydactyly; Diarrhea 3, secretory sodium, congenital, syndromic, 270420; hexadactyly
Limb disorders v0.179 SPINT2 Rebecca Foulger Phenotypes for gene: SPINT2 were changed from Polydactyly to Polydactyly; Diarrhea 3, secretory sodium, congenital, syndromic, 270420; hexadactyly
Limb disorders v0.178 SPINT2 Rebecca Foulger Added comment: Comment on mode of inheritance: Biallelic MOI supported by OMIM and literature (PMIDs:19185281,24142340).
Limb disorders v0.178 SPINT2 Rebecca Foulger Mode of inheritance for gene: SPINT2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.177 SPINT2 Rebecca Foulger Publications for gene: SPINT2 were set to
Limb disorders v0.176 SMO Rebecca Foulger commented on gene: SMO: PMID:27236920 (Twigg et al, 2016) analysed 10 unrelated patients with Curry-Jones syndrome including 6 previously reported patients. They identified somatic mosaicism for the identical L412F variant in SMO in 8 of the patients. The patients all showed cutaneous syndactyly and/or preaxial polydactyly.
Limb disorders v0.176 SMO Rebecca Foulger Phenotypes for gene: SMO were changed from Polydactyly to Polydactyly; Curry-Jones syndrome, somatic mosaic, MIM:601500; Cutaneous syndactyly; Preaxial polydactyly
Limb disorders v0.175 SMO Rebecca Foulger Publications for gene: SMO were set to
Limb disorders v0.174 SMO Rebecca Foulger Added comment: Comment on mode of pathogenicity: Somatic mosaicism.
Limb disorders v0.174 SMO Rebecca Foulger Mode of pathogenicity for gene: SMO was changed from None to Other
Limb disorders v0.173 SMO Rebecca Foulger commented on gene: SMO
Limb disorders v0.173 SMO Rebecca Foulger Tag mosaicism tag was added to gene: SMO.
Limb disorders v0.173 ALMS1 Eleanor Williams Classified gene: ALMS1 as Red List (low evidence)
Limb disorders v0.173 ALMS1 Eleanor Williams Added comment: Comment on list classification: Rating red as only one report of a variant in this gene being associated with a polydactyly phenotype.
Limb disorders v0.173 ALMS1 Eleanor Williams Gene: alms1 has been classified as Red List (Low Evidence).
Limb disorders v0.172 ALMS1 Eleanor Williams edited their review of gene: ALMS1: Changed publications: 24400638
Limb disorders v0.172 ALMS1 Eleanor Williams commented on gene: ALMS1
Limb disorders v0.172 AKT3 Eleanor Williams commented on gene: AKT3: Consulting with the Genomics England clinical team as to the appropriate rating of this gene.
Limb disorders v0.172 AHI1 Eleanor Williams edited their review of gene: AHI1: Changed publications: 17377524, 1341417; Changed phenotypes: Joubert syndrome 3 608629
Limb disorders v0.172 AKT3 Eleanor Williams edited their review of gene: AKT3: Changed publications: 23592320, 22729224, 23745724, 22500628, 22729223; Changed phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 615937
Limb disorders v0.172 AKT3 Eleanor Williams commented on gene: AKT3
Limb disorders v0.172 AHI1 Eleanor Williams commented on gene: AHI1: Checking with Genomics England clinical team whether the Jouberts Syndrome is a relevant phenotype for this panel.
Limb disorders v0.172 AHI1 Eleanor Williams commented on gene: AHI1
Limb disorders v0.172 BMP2 Eleanor Williams Classified gene: BMP2 as Green List (high evidence)
Limb disorders v0.172 BMP2 Eleanor Williams Added comment: Comment on list classification: Rating as green as publication PMID:29198724 reports sufficient cases associated with a relevant phenotype to reach a green rating for SNVs. The skeletal features include phalangeal anomalies. Rating has been checked with the Genomics England clinical team.
Limb disorders v0.172 BMP2 Eleanor Williams Gene: bmp2 has been classified as Green List (High Evidence).
Limb disorders v0.171 BMP2 Eleanor Williams Tag cnv tag was added to gene: BMP2.
Limb disorders v0.171 ZSWIM6 Sarah Leigh Tag missense tag was added to gene: ZSWIM6.
Limb disorders v0.171 ZSWIM6 Sarah Leigh Mode of pathogenicity for gene: ZSWIM6 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Limb disorders v0.170 WDPCP Sarah Leigh Marked gene: WDPCP as ready
Limb disorders v0.170 WDPCP Sarah Leigh Added comment: Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified in a single case.
Limb disorders v0.170 WDPCP Sarah Leigh Gene: wdpcp has been classified as Red List (Low Evidence).
Limb disorders v0.170 WDPCP Sarah Leigh Publications for gene: WDPCP were set to
Limb disorders v0.169 WDPCP Sarah Leigh Mode of inheritance for gene: WDPCP was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.168 WDPCP Sarah Leigh Phenotypes for gene: WDPCP were changed from Polydactyly to ?Congenital heart defects, hamartomas of tongue, and polysyndactyly 217085
Limb disorders v0.167 WDR19 Sarah Leigh Marked gene: WDR19 as ready
Limb disorders v0.167 WDR19 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. Two variants reported as compound heterozygotes in affected members of one family with Cranioectodermal dysplasia 4 and one homozygous variant reported in Short-rib thoracic dysplasia 5 without polydactyly 614376, but this phenotype also includes brachydactyly.
Limb disorders v0.167 WDR19 Sarah Leigh Gene: wdr19 has been classified as Red List (Low Evidence).
Limb disorders v0.167 WDR19 Sarah Leigh Mode of inheritance for gene: WDR19 was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.166 WDR19 Sarah Leigh Added comment: Comment on phenotypes: Variants also reported in Nephronophthisis 13 614377 & Senior-Loken syndrome 8 616307, but these phenotypes are not relevant to the limb disorders panel
Limb disorders v0.166 WDR19 Sarah Leigh Phenotypes for gene: WDR19 were changed from ?Cranioectodermal dysplasia 4 614378; ?Short-rib thoracic dysplasia 5 with or without polydactyly 614376 to ?Cranioectodermal dysplasia 4 614378; ?Short-rib thoracic dysplasia 5 with or without polydactyly 614376
Limb disorders v0.165 WDR19 Sarah Leigh Publications for gene: WDR19 were set to
Limb disorders v0.164 WDR19 Sarah Leigh Phenotypes for gene: WDR19 were changed from Polydactyly to ?Cranioectodermal dysplasia 4 614378; ?Short-rib thoracic dysplasia 5 with or without polydactyly 614376
Limb disorders v0.163 WDR34 Sarah Leigh Marked gene: WDR34 as ready
Limb disorders v0.163 WDR34 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Short-rib thoracic dysplasia 11 with or without polydactyly 615633 and severe asphyxiating thoracic dysplasia. Although polydactyly is not commonly recorded in this phenotype, the majority of cases have shorted limbs, such that PMID 24183451 reports 5 variants in 4 unrelated cases with short limbs.
Limb disorders v0.163 WDR34 Sarah Leigh Gene: wdr34 has been classified as Green List (High Evidence).
Limb disorders v0.163 WDR34 Sarah Leigh Phenotypes for gene: WDR34 were changed from Short-rib thoracic dysplasia 11 with or without polydactyly 615633 to Short-rib thoracic dysplasia 11 with or without polydactyly 615633; severe asphyxiating thoracic dysplasia
Limb disorders v0.162 WDR34 Sarah Leigh Publications for gene: WDR34 were set to
Limb disorders v0.161 WDR34 Sarah Leigh Classified gene: WDR34 as Green List (high evidence)
Limb disorders v0.161 WDR34 Sarah Leigh Gene: wdr34 has been classified as Green List (High Evidence).
Limb disorders v0.160 WDR34 Sarah Leigh Phenotypes for gene: WDR34 were changed from Polydactyly to Short-rib thoracic dysplasia 11 with or without polydactyly 615633
Limb disorders v0.159 WDR34 Sarah Leigh Mode of inheritance for gene: WDR34 was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.158 WDR35 Sarah Leigh Classified gene: WDR35 as Green List (high evidence)
Limb disorders v0.158 WDR35 Sarah Leigh Gene: wdr35 has been classified as Green List (High Evidence).
Limb disorders v0.157 WDR35 Sarah Leigh Marked gene: WDR35 as ready
Limb disorders v0.157 WDR35 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotypes in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in Cranioectodermal dysplasia 2 613610 and 7 variants reported in Short-rib thoracic dysplasia 7 with or without polydactyly 614091. Both phenotypes are relevant to this panel, supportive evidence also provided from a mouse model (PMID 21473986).
Limb disorders v0.157 WDR35 Sarah Leigh Gene: wdr35 has been classified as Red List (Low Evidence).
Limb disorders v0.157 WDR35 Sarah Leigh Publications for gene: WDR35 were set to
Limb disorders v0.156 WDR35 Sarah Leigh Phenotypes for gene: WDR35 were changed from Polydactyly to Cranioectodermal dysplasia 2 613610; Short-rib thoracic dysplasia 7 with or without polydactyly 614091
Limb disorders v0.155 WDR35 Sarah Leigh Mode of inheritance for gene: WDR35 was changed from to BIALLELIC, autosomal or pseudoautosomal
Limb disorders v0.154 ZSWIM6 Sarah Leigh Classified gene: ZSWIM6 as Amber List (moderate evidence)
Limb disorders v0.154 ZSWIM6 Sarah Leigh Gene: zswim6 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.153 ZSWIM6 Sarah Leigh commented on gene: ZSWIM6
Limb disorders v0.153 ZSWIM6 Sarah Leigh Tag mosaicism tag was added to gene: ZSWIM6.
Limb disorders v0.153 ZSWIM6 Sarah Leigh Publications for gene: ZSWIM6 were set to
Limb disorders v0.152 ZSWIM6 Sarah Leigh Phenotypes for gene: ZSWIM6 were changed from Polydactyly to Acromelic frontonasal dysostosis 603671
Limb disorders v0.151 ZSWIM6 Sarah Leigh Mode of inheritance for gene: ZSWIM6 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.150 MIR17HG Eleanor Williams Phenotypes for gene: MIR17HG were changed from to Feingold syndrome 2 614326
Limb disorders v0.149 FGF9 Eleanor Williams Added comment: Comment on mode of inheritance: Both cases to date report monoallelic inheritance
Limb disorders v0.149 FGF9 Eleanor Williams Mode of inheritance for gene: FGF9 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.148 BMP2 Eleanor Williams Added comment: Comment on publications: Added PMID:29129813 another report from 2018 of a duplication downstream of BMP2 in a Chinese family with Brachydactyly type A2
Limb disorders v0.148 BMP2 Eleanor Williams Publications for gene: BMP2 were set to 19327734; 21357617; 29198724
Limb disorders v0.147 BHLHA9 Eleanor Williams commented on gene: BHLHA9
Limb disorders v0.147 ARHGAP31 Eleanor Williams commented on gene: ARHGAP31: PMID: 21565291 (Southgate et al 2011) report that the two variants found have a gain of function.
Limb disorders v0.147 ARHGAP31 Eleanor Williams commented on gene: ARHGAP31
Limb disorders v0.147 ARHGAP31 Eleanor Williams Publications for gene: ARHGAP31 were set to 21565291
Limb disorders v0.146 ZNF141 Eleanor Williams commented on gene: ZNF141
Limb disorders v0.146 SOX9 Eleanor Williams commented on gene: SOX9
Limb disorders v0.146 SLC25A21 Eleanor Williams commented on gene: SLC25A21
Limb disorders v0.146 SHH Eleanor Williams commented on gene: SHH
Limb disorders v0.146 POLL Eleanor Williams commented on gene: POLL: Genomics England clinical team notes - Agree with red rating. Part of the critical region of a duplication identified in split hand/foot malformation; no direct evidence this is the causative gene
Limb disorders v0.146 MIPOL1 Eleanor Williams commented on gene: MIPOL1
Limb disorders v0.146 IQCE Eleanor Williams commented on gene: IQCE
Limb disorders v0.146 GREM1 Eleanor Williams commented on gene: GREM1
Limb disorders v0.146 KIAA0586 Eleanor Williams commented on gene: KIAA0586
Limb disorders v0.146 IFT43 Eleanor Williams commented on gene: IFT43
Limb disorders v0.146 DYNC2H1 Eleanor Williams commented on gene: DYNC2H1
Limb disorders v0.146 TRPV4 Eleanor Williams commented on gene: TRPV4
Limb disorders v0.146 SMOC1 Eleanor Williams commented on gene: SMOC1
Limb disorders v0.146 SLC26A2 Eleanor Williams commented on gene: SLC26A2
Limb disorders v0.146 SFRP4 Eleanor Williams commented on gene: SFRP4
Limb disorders v0.146 PRMT7 Eleanor Williams commented on gene: PRMT7: Genomics England clinical team notes - Not primarily limb phenotype (skeletal dysplasia + ID), on appropriate panels.
Limb disorders v0.146 PRMT7 Eleanor Williams Classified gene: PRMT7 as Amber List (moderate evidence)
Limb disorders v0.146 PRMT7 Eleanor Williams Added comment: Comment on list classification: Rated Amber after review by Genomics England clinical team
Limb disorders v0.146 PRMT7 Eleanor Williams Gene: prmt7 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.145 PORCN Eleanor Williams commented on gene: PORCN: Genomics England clinical team notes - Not primarily limb (focal dermal hypoplasia/Goltz Gorlin)
Limb disorders v0.145 PORCN Eleanor Williams Classified gene: PORCN as Amber List (moderate evidence)
Limb disorders v0.145 PORCN Eleanor Williams Added comment: Comment on list classification: Rated Amber after review by Genomics England clinical team
Limb disorders v0.145 PORCN Eleanor Williams Gene: porcn has been classified as Amber List (Moderate Evidence).
Limb disorders v0.144 PDE3A Eleanor Williams commented on gene: PDE3A
Limb disorders v0.144 NEK1 Eleanor Williams commented on gene: NEK1: Genomics England clinical team notes - Not primarily limb - short rib +/- polydactyly (ciliopathy). On ciliopathy, skeletal dysplasia, clefting and thoracic dystrophies panels already
Limb disorders v0.144 NEK1 Eleanor Williams Classified gene: NEK1 as Amber List (moderate evidence)
Limb disorders v0.144 NEK1 Eleanor Williams Added comment: Comment on list classification: Rated Amber after review by Genomics England clinical team
Limb disorders v0.144 NEK1 Eleanor Williams Gene: nek1 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.143 LRP4 Eleanor Williams commented on gene: LRP4
Limb disorders v0.143 COL2A1 Eleanor Williams commented on gene: COL2A1: Genomics England clinical team notes - Not primarily limb. On clefting, skeletal dysplasia panels.
Limb disorders v0.143 COL2A1 Eleanor Williams Classified gene: COL2A1 as Amber List (moderate evidence)
Limb disorders v0.143 COL2A1 Eleanor Williams Added comment: Comment on list classification: Rated Amber after review by Genomics England clinical team
Limb disorders v0.143 COL2A1 Eleanor Williams Gene: col2a1 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.142 CHSY1 Eleanor Williams commented on gene: CHSY1: Genomics England Clinical team notes - Not primarily limb (Temtamy Preaxial brachydactyly syndrome). Already on skeletal dysplasia panel
Limb disorders v0.142 CHSY1 Eleanor Williams Classified gene: CHSY1 as Amber List (moderate evidence)
Limb disorders v0.142 CHSY1 Eleanor Williams Added comment: Comment on list classification: Rated Amber after review from Genomics England clinical team
Limb disorders v0.142 CHSY1 Eleanor Williams Gene: chsy1 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.141 ORC1 Eleanor Williams commented on gene: ORC1: Genomics England clinical team notes - Limb not isolated phenotype (Meier-Gorlin), on appropriate panels
Limb disorders v0.141 TRAPPC2 Eleanor Williams commented on gene: TRAPPC2: Genomics England clinical team notes - Presents with short stature (MEDT), on skeletal dysplasia panel
Limb disorders v0.141 TRAPPC2 Eleanor Williams Classified gene: TRAPPC2 as Amber List (moderate evidence)
Limb disorders v0.141 TRAPPC2 Eleanor Williams Added comment: Comment on list classification: Rated Amber on advice from Genomics England clinical team
Limb disorders v0.141 TRAPPC2 Eleanor Williams Gene: trappc2 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.140 ORC1 Eleanor Williams Classified gene: ORC1 as Amber List (moderate evidence)
Limb disorders v0.140 ORC1 Eleanor Williams Added comment: Comment on list classification: Rated Amber on advice on Genomics England clinical team. Limb not isolated phenotype (Meier-Gorlin) on appropriate panels
Limb disorders v0.140 ORC1 Eleanor Williams Gene: orc1 has been classified as Amber List (Moderate Evidence).
Limb disorders SLX4 Ellen McDonagh Added gene to panel
Limb disorders RPS7 Ellen McDonagh Added gene to panel
Limb disorders RPS29 Ellen McDonagh Added gene to panel
Limb disorders RPS28 Ellen McDonagh Added gene to panel
Limb disorders RPS26 Ellen McDonagh Added gene to panel
Limb disorders RPS24 Ellen McDonagh Added gene to panel
Limb disorders RPS19 Ellen McDonagh Added gene to panel
Limb disorders RPS17 Ellen McDonagh Added gene to panel
Limb disorders RPS10 Ellen McDonagh Added gene to panel
Limb disorders RPL5 Ellen McDonagh Added gene to panel
Limb disorders RPL35A Ellen McDonagh Added gene to panel
Limb disorders RPL26 Ellen McDonagh Added gene to panel
Limb disorders RPL11 Ellen McDonagh Added gene to panel
Limb disorders RAD51C Ellen McDonagh Added gene to panel
Limb disorders PALB2 Ellen McDonagh Added gene to panel
Limb disorders GATA1 Ellen McDonagh Added gene to panel
Limb disorders FANCM Ellen McDonagh Added gene to panel
Limb disorders FANCL Ellen McDonagh Added gene to panel
Limb disorders FANCI Ellen McDonagh Added gene to panel
Limb disorders FANCG Ellen McDonagh Added gene to panel
Limb disorders FANCF Ellen McDonagh Added gene to panel
Limb disorders FANCE Ellen McDonagh Added gene to panel
Limb disorders FANCD2 Ellen McDonagh Added gene to panel
Limb disorders FANCC Ellen McDonagh Added gene to panel
Limb disorders FANCB Ellen McDonagh Added gene to panel
Limb disorders FANCA Ellen McDonagh Added gene to panel
Limb disorders ERCC4 Ellen McDonagh Added gene to panel
Limb disorders BRIP1 Ellen McDonagh Added gene to panel
Limb disorders BRCA2 Ellen McDonagh Added gene to panel
Limb disorders ZSWIM6 Ellen McDonagh Added gene to panel
Limb disorders WDR35 Ellen McDonagh Added gene to panel
Limb disorders WDR34 Ellen McDonagh Added gene to panel
Limb disorders WDR19 Ellen McDonagh Added gene to panel
Limb disorders WDPCP Ellen McDonagh Added gene to panel
Limb disorders USP9X Ellen McDonagh Added gene to panel
Limb disorders UBE3B Ellen McDonagh Added gene to panel
Limb disorders TWIST1 Ellen McDonagh Added gene to panel
Limb disorders TTC8 Ellen McDonagh Added gene to panel
Limb disorders TTC21B Ellen McDonagh Added gene to panel
Limb disorders TRIM32 Ellen McDonagh Added gene to panel
Limb disorders TRAF3IP1 Ellen McDonagh Added gene to panel
Limb disorders TMEM237 Ellen McDonagh Added gene to panel
Limb disorders TMEM231 Ellen McDonagh Added gene to panel
Limb disorders TMEM216 Ellen McDonagh Added gene to panel
Limb disorders TMEM138 Ellen McDonagh Added gene to panel
Limb disorders TFAP2B Ellen McDonagh Added gene to panel
Limb disorders TFAP2A Ellen McDonagh Added gene to panel
Limb disorders TCTN3 Ellen McDonagh Added gene to panel
Limb disorders TCTN2 Ellen McDonagh Added gene to panel
Limb disorders TCTEX1D2 Ellen McDonagh Added gene to panel
Limb disorders TBX22 Ellen McDonagh Added gene to panel
Limb disorders SPINT2 Ellen McDonagh Added gene to panel
Limb disorders SMO Ellen McDonagh Added gene to panel
Limb disorders SDCCAG8 Ellen McDonagh Added gene to panel
Limb disorders SC5D Ellen McDonagh Added gene to panel
Limb disorders RBM10 Ellen McDonagh Added gene to panel
Limb disorders PROM1 Ellen McDonagh Added gene to panel
Limb disorders PNPLA6 Ellen McDonagh Added gene to panel
Limb disorders PIK3R2 Ellen McDonagh Added gene to panel
Limb disorders PIK3CA Ellen McDonagh Added gene to panel
Limb disorders PDE6D Ellen McDonagh Added gene to panel
Limb disorders NPHP3 Ellen McDonagh Added gene to panel
Limb disorders MKKS Ellen McDonagh Added gene to panel
Limb disorders MEGF8 Ellen McDonagh Added gene to panel
Limb disorders MBTPS2 Ellen McDonagh Added gene to panel
Limb disorders LZTFL1 Ellen McDonagh Added gene to panel
Limb disorders LBR Ellen McDonagh Added gene to panel
Limb disorders INPP5E Ellen McDonagh Added gene to panel
Limb disorders IFT80 Ellen McDonagh Added gene to panel
Limb disorders IFT52 Ellen McDonagh Added gene to panel
Limb disorders IFT27 Ellen McDonagh Added gene to panel
Limb disorders IFT172 Ellen McDonagh Added gene to panel
Limb disorders IFT140 Ellen McDonagh Added gene to panel
Limb disorders ICK Ellen McDonagh Added gene to panel
Limb disorders HYLS1 Ellen McDonagh Added gene to panel
Limb disorders HNRNPK Ellen McDonagh Added gene to panel
Limb disorders GRIP1 Ellen McDonagh Added gene to panel
Limb disorders GPC3 Ellen McDonagh Added gene to panel
Limb disorders GLI2 Ellen McDonagh Added gene to panel
Limb disorders FREM2 Ellen McDonagh Added gene to panel
Limb disorders FRAS1 Ellen McDonagh Added gene to panel
Limb disorders EVC2 Ellen McDonagh Added gene to panel
Limb disorders EVC Ellen McDonagh Added gene to panel
Limb disorders EBP Ellen McDonagh Added gene to panel
Limb disorders DYNC2LI1 Ellen McDonagh Added gene to panel
Limb disorders DDX59 Ellen McDonagh Added gene to panel
Limb disorders CSPP1 Ellen McDonagh Added gene to panel
Limb disorders CKAP2L Ellen McDonagh Added gene to panel
Limb disorders CEP41 Ellen McDonagh Added gene to panel
Limb disorders CEP164 Ellen McDonagh Added gene to panel
Limb disorders CEP120 Ellen McDonagh Added gene to panel
Limb disorders CENPF Ellen McDonagh Added gene to panel
Limb disorders CD96 Ellen McDonagh Added gene to panel
Limb disorders CCND2 Ellen McDonagh Added gene to panel
Limb disorders C5orf42 Ellen McDonagh Added gene to panel
Limb disorders C2CD3 Ellen McDonagh Added gene to panel
Limb disorders BMP4 Ellen McDonagh Added gene to panel
Limb disorders BBS9 Ellen McDonagh Added gene to panel
Limb disorders BBS7 Ellen McDonagh Added gene to panel
Limb disorders BBS5 Ellen McDonagh Added gene to panel
Limb disorders BBS4 Ellen McDonagh Added gene to panel
Limb disorders BBS2 Ellen McDonagh Added gene to panel
Limb disorders BBS12 Ellen McDonagh Added gene to panel
Limb disorders BBS10 Ellen McDonagh Added gene to panel
Limb disorders BBS1 Ellen McDonagh Added gene to panel
Limb disorders B9D2 Ellen McDonagh Added gene to panel
Limb disorders B9D1 Ellen McDonagh Added gene to panel
Limb disorders ARMC8 Ellen McDonagh Added gene to panel
Limb disorders ARL6 Ellen McDonagh Added gene to panel
Limb disorders ALX3 Ellen McDonagh Added gene to panel
Limb disorders ALMS1 Ellen McDonagh Added gene to panel
Limb disorders AKT3 Ellen McDonagh Added gene to panel
Limb disorders AHI1 Ellen McDonagh Added gene to panel
Limb disorders SOX9 Rachel Jones reviewed SOX9
Limb disorders SLC25A21 Rachel Jones reviewed SLC25A21
Limb disorders SHH Rachel Jones reviewed SHH
Limb disorders IQCE Rachel Jones reviewed IQCE
Limb disorders GREM1 Rachel Jones reviewed GREM1
Limb disorders MIPOL1 Rachel Jones reviewed MIPOL1
Limb disorders SOX9 Ellen McDonagh Added gene to panel
Limb disorders SMOC1 Ellen McDonagh classified SMOC1 as Green List (high evidence)
Limb disorders SMOC1 Ellen McDonagh Added gene to panel
Limb disorders PORCN Ellen McDonagh classified PORCN as Green List (high evidence)
Limb disorders PORCN Ellen McDonagh classified PORCN as Red List (low evidence)
Limb disorders PORCN Ellen McDonagh Added gene to panel
Limb disorders TRPV4 Ellen McDonagh classified TRPV4 as Green List (high evidence)
Limb disorders TRPV4 Ellen McDonagh Added gene to panel
Limb disorders SLC26A2 Ellen McDonagh classified SLC26A2 as Green List (high evidence)
Limb disorders SLC26A2 Ellen McDonagh Added gene to panel
Limb disorders PRMT7 Ellen McDonagh classified PRMT7 as Green List (high evidence)
Limb disorders PRMT7 Ellen McDonagh classified PRMT7 as Red List (low evidence)
Limb disorders PRMT7 Ellen McDonagh Added gene to panel
Limb disorders PDE3A Ellen McDonagh classified PDE3A as Green List (high evidence)
Limb disorders PDE3A Ellen McDonagh Added gene to panel
Limb disorders SLC25A21 Ellen McDonagh classified SLC25A21 as Red List (low evidence)
Limb disorders SLC25A21 Ellen McDonagh Added gene to panel
Limb disorders MIPOL1 Ellen McDonagh marked MIPOL1 as ready
Limb disorders MIPOL1 Ellen McDonagh classified MIPOL1 as Red List (low evidence)
Limb disorders MIPOL1 Ellen McDonagh Added gene to panel
Limb disorders ZNF141 Ellen McDonagh Added gene to panel
Limb disorders KIAA0586 Ellen McDonagh classified KIAA0586 as Amber List (moderate evidence)
Limb disorders KIAA0586 Ellen McDonagh Added gene to panel
Limb disorders IQCE Ellen McDonagh marked IQCE as ready
Limb disorders IQCE Ellen McDonagh classified IQCE as Red List (low evidence)
Limb disorders IQCE Ellen McDonagh Added gene to panel
Limb disorders NEK1 Ellen McDonagh classified NEK1 as Green List (high evidence)
Limb disorders NEK1 Ellen McDonagh Added gene to panel
Limb disorders DYNC2H1 Ellen McDonagh classified DYNC2H1 as Amber List (moderate evidence)
Limb disorders DYNC2H1 Ellen McDonagh Added gene to panel
Limb disorders IFT43 Ellen McDonagh classified IFT43 as Amber List (moderate evidence)
Limb disorders IFT43 Ellen McDonagh Added gene to panel
Limb disorders COL2A1 Ellen McDonagh classified COL2A1 as Green List (high evidence)
Limb disorders COL2A1 Ellen McDonagh Added gene to panel
Limb disorders CHSY1 Ellen McDonagh classified CHSY1 as Green List (high evidence)
Limb disorders CHSY1 Ellen McDonagh Added gene to panel
Limb disorders SFRP4 Ellen McDonagh classified SFRP4 as Green List (high evidence)
Limb disorders FGF9 Ellen McDonagh classified FGF9 as Amber List (moderate evidence)
Limb disorders FGD1 Ellen McDonagh classified FGD1 as Amber List (moderate evidence)
Limb disorders SFRP4 Ellen McDonagh classified SFRP4 as Amber List (moderate evidence)
Limb disorders SFRP4 Ellen McDonagh Added gene to panel
Limb disorders DVL2 Ellen McDonagh commented on DVL2
Limb disorders DVL3 Sarah Leigh classified DVL3 as Green List (high evidence)
Limb disorders FGD1 Olivia Niblock reviewed FGD1
Limb disorders MIR17HG Sarah Leigh classified MIR17HG as Amber List (moderate evidence)
Limb disorders FBLN1 Sarah Leigh edited their review of FBLN1
Limb disorders FBLN1 Sarah Leigh classified FBLN1 as Amber List (moderate evidence)
Limb disorders POLL Eleanor Williams edited their review of POLL
Limb disorders LRP4 Louise Daugherty classified LRP4 as Green List (high evidence)
Limb disorders POLL Eleanor Williams classified POLL as Red List (low evidence)
Limb disorders LRP4 Louise Daugherty edited their review of LRP4
Limb disorders LRP4 Louise Daugherty commented on LRP4
Limb disorders LRP4 Louise Daugherty Added gene to panel
Limb disorders FGF9 Olivia Niblock reviewed FGF9
Limb disorders FMN1 Louise Daugherty reviewed FMN1
Limb disorders EFTUD2 Sarah Leigh edited their review of EFTUD2
Limb disorders NOTCH1 Louise Daugherty classified NOTCH1 as Green List (high evidence)
Limb disorders EFTUD2 Sarah Leigh classified EFTUD2 as Green List (high evidence)
Limb disorders DVL2 Sarah Leigh commented on DVL2
Limb disorders DLL4 Sarah Leigh commented on DLL4
Limb disorders GREM1 Olivia Niblock reviewed GREM1
Limb disorders BMP2 Ellen McDonagh classified BMP2 as Amber List (moderate evidence)
Limb disorders DLL4 Sarah Leigh classified DLL4 as Green List (high evidence)
Limb disorders SHH Sarah Leigh edited their review of SHH
Limb disorders DLX5 Louise Daugherty reviewed DLX5
Limb disorders SEM1 Louise Daugherty edited their review of SEM1
Limb disorders SEM1 Louise Daugherty commented on SEM1
Limb disorders DLX6 Louise Daugherty edited their review of DLX6
Limb disorders DLX6 Louise Daugherty reviewed DLX6
Limb disorders TRAPPC2 Ellen McDonagh Added gene to panel
Limb disorders ORC1 Ellen McDonagh Added gene to panel
Limb disorders POLL Ellen McDonagh Added gene to panel
Limb disorders BTRC Ellen McDonagh classified BTRC as Amber List (moderate evidence)
Limb disorders BTRC Ellen McDonagh classified BTRC as Red List (low evidence)
Limb disorders SHH Ellen McDonagh classified SHH as Red List (low evidence)
Limb disorders SHH Dimitris Polychronopoulos Added gene to panel
Limb disorders FAM58A Ellen McDonagh commented on FAM58A
Limb disorders SEM1 Ellen McDonagh commented on SEM1
Limb disorders WNT7A Ellen McDonagh Added gene to panel
Limb disorders WNT5A Ellen McDonagh Added gene to panel
Limb disorders WNT10B Ellen McDonagh Added gene to panel
Limb disorders WDR60 Ellen McDonagh Added gene to panel
Limb disorders TRPS1 Ellen McDonagh Added gene to panel
Limb disorders TP63 Ellen McDonagh Added gene to panel
Limb disorders TMEM67 Ellen McDonagh Added gene to panel
Limb disorders TBX5 Ellen McDonagh Added gene to panel
Limb disorders TBX4 Ellen McDonagh Added gene to panel
Limb disorders TBX3 Ellen McDonagh Added gene to panel
Limb disorders SMC3 Ellen McDonagh Added gene to panel
Limb disorders SMC1A Ellen McDonagh Added gene to panel
Limb disorders SEM1 Ellen McDonagh Added gene to panel
Limb disorders SF3B4 Ellen McDonagh Added gene to panel
Limb disorders SALL4 Ellen McDonagh Added gene to panel
Limb disorders SALL1 Ellen McDonagh Added gene to panel
Limb disorders RPGRIP1L Ellen McDonagh Added gene to panel
Limb disorders ROR2 Ellen McDonagh Added gene to panel
Limb disorders RNU4ATAC Ellen McDonagh Added gene to panel
Limb disorders RECQL4 Ellen McDonagh Added gene to panel
Limb disorders RBPJ Ellen McDonagh Added gene to panel
Limb disorders RBM8A Ellen McDonagh Added gene to panel
Limb disorders RAB23 Ellen McDonagh Added gene to panel
Limb disorders PTHLH Ellen McDonagh Added gene to panel
Limb disorders PITX1 Ellen McDonagh Added gene to panel
Limb disorders PCNT Ellen McDonagh Added gene to panel
Limb disorders OFD1 Ellen McDonagh Added gene to panel
Limb disorders NOTCH1 Ellen McDonagh Added gene to panel
Limb disorders NOG Ellen McDonagh Added gene to panel
Limb disorders NIPBL Ellen McDonagh Added gene to panel
Limb disorders MYCN Ellen McDonagh Added gene to panel
Limb disorders MKS1 Ellen McDonagh Added gene to panel
Limb disorders MIR17HG Ellen McDonagh Added gene to panel
Limb disorders LMX1B Ellen McDonagh Added gene to panel
Limb disorders LMBR1 Ellen McDonagh Added gene to panel
Limb disorders KIF7 Ellen McDonagh Added gene to panel
Limb disorders IHH Ellen McDonagh Added gene to panel
Limb disorders HOXD13 Ellen McDonagh Added gene to panel
Limb disorders HOXA13 Ellen McDonagh Added gene to panel
Limb disorders HDAC4 Ellen McDonagh Added gene to panel
Limb disorders GREM1 Ellen McDonagh Added gene to panel
Limb disorders GNAS Ellen McDonagh Added gene to panel
Limb disorders GLI3 Ellen McDonagh Added gene to panel
Limb disorders GJA1 Ellen McDonagh Added gene to panel
Limb disorders GDF5 Ellen McDonagh Added gene to panel
Limb disorders FMN1 Ellen McDonagh Added gene to panel
Limb disorders FLNA Ellen McDonagh Added gene to panel
Limb disorders FGFR3 Ellen McDonagh Added gene to panel
Limb disorders FGFR2 Ellen McDonagh Added gene to panel
Limb disorders FGFR1 Ellen McDonagh Added gene to panel
Limb disorders FGF9 Ellen McDonagh Added gene to panel
Limb disorders FGF16 Ellen McDonagh Added gene to panel
Limb disorders FGF10 Ellen McDonagh Added gene to panel
Limb disorders FGD1 Ellen McDonagh Added gene to panel
Limb disorders FBLN1 Ellen McDonagh Added gene to panel
Limb disorders FAM58A Ellen McDonagh Added gene to panel
Limb disorders EOGT Ellen McDonagh Added gene to panel
Limb disorders EFTUD2 Ellen McDonagh Added gene to panel
Limb disorders DVL3 Ellen McDonagh Added gene to panel
Limb disorders DVL2 Ellen McDonagh Added gene to panel
Limb disorders DVL1 Ellen McDonagh Added gene to panel
Limb disorders DOCK6 Ellen McDonagh Added gene to panel
Limb disorders DLX6 Ellen McDonagh Added gene to panel
Limb disorders DLX5 Ellen McDonagh Added gene to panel
Limb disorders DLL4 Ellen McDonagh Added gene to panel
Limb disorders CEP290 Ellen McDonagh Added gene to panel
Limb disorders CC2D2A Ellen McDonagh Added gene to panel
Limb disorders BTRC Ellen McDonagh Added gene to panel
Limb disorders BMPR1B Ellen McDonagh Added gene to panel
Limb disorders BMP2 Ellen McDonagh Added gene to panel
Limb disorders BHLHA9 Ellen McDonagh Added gene to panel
Limb disorders ARSE Ellen McDonagh Added gene to panel
Limb disorders ARHGAP31 Ellen McDonagh Added gene to panel