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Osteogenesis imperfecta v5.3 KIF5B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: KIF5B.
Osteogenesis imperfecta v5.3 KIF5B Ida Ertmanska Tag Q3_24_promote_green was removed from gene: KIF5B.
Osteogenesis imperfecta v5.3 KIF5B Ida Ertmanska reviewed gene: KIF5B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v5.2 KIF5B Ida Ertmanska Source NHS GMS was added to KIF5B.
Source Expert Review Green was added to KIF5B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Osteogenesis imperfecta v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2025-04-30
Osteogenesis imperfecta v5.0 Eleanor Williams promoted panel to version 5.0
Osteogenesis imperfecta v4.9 WNT11 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WNT11.
Osteogenesis imperfecta v4.9 WNT11 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: WNT11.
Osteogenesis imperfecta v4.9 WNT11 Achchuthan Shanmugasundram commented on gene: WNT11: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Osteogenesis imperfecta v4.8 WNT11 Achchuthan Shanmugasundram Source NHS GMS was added to WNT11.
Source Expert Review Green was added to WNT11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Osteogenesis imperfecta v4.7 KIF5B Achchuthan Shanmugasundram Classified gene: KIF5B as Amber List (moderate evidence)
Osteogenesis imperfecta v4.7 KIF5B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases) for the promotion of this gene to green rating in the next GMS update.
Osteogenesis imperfecta v4.7 KIF5B Achchuthan Shanmugasundram Gene: kif5b has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v4.6 KIF5B Achchuthan Shanmugasundram gene: KIF5B was added
gene: KIF5B was added to Osteogenesis imperfecta. Sources: Literature
Q3_24_promote_green tags were added to gene: KIF5B.
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to 37934770
Phenotypes for gene: KIF5B were set to osteogenesis imperfecta, MONDO:0019019
Review for gene: KIF5B was set to GREEN
Added comment: PMID:37934770 reported the identification of three distinct de novo heterozygous KIF5B variants (p.Thr87Ile, p.Gly90Ala and p.Thr195Lys) in four unrelated individuals with osteogenesis imperfecta (OI). All these variants are present within the highly conserved kinesis motor domain. Functional studies in C. elegans, human cell lines and bone biopsy show impaired protein function and suggest dominant negative mechanism for variants. It is not clear what distinguishes OI phenotypes from other phenotypes for this gene reported in PMIDs: 35342932 and 36018820.
Sources: Literature
Osteogenesis imperfecta v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Osteogenesis imperfecta v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Osteogenesis imperfecta v3.7 WNT11 Achchuthan Shanmugasundram changed review comment from: Comment on gene classification: The rating of this gene can be added as green as this gene has been implicated in early-onset osteoporosis from three unrelated cases and was supported by evidence from functional studies. All three patients harboured heterozygous variants in WNT11 gene.

Three unrelated cases are reported in PMID: 34875064. A four year-old boy harbouring de novo heterozygous loss-of-function variant c.677_678dupGG (p.Leu227Glyfs*22) was reported with low BMD, osteopenia and several fractures.

A 51 year-old woman and her 69 year-old mother were identified with a heterozygous missense variant c.217G>A (p.Ala73Thr). The woman was reported with bone fragility, several fractures, osteoarthritis and osteoporosis, while her mother also had several osteoporotic fractures.

A 61 year-old woman that was reported with lumbar spine osteoarthritis had several fractures since 55 years of age was identified with a heterozygous missense variant c.865G>A (p.Val289Met).

This was also supported by results from functional studies, where cell lines with the loss-of-function variant generated by CRISPR-Cas9 showed reduced cell proliferation and osteoblast differentiation in comparison to wild-type. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells.
Sources: Literature; to: Comment on gene classification: The rating of this gene can be added as green as this gene has been implicated in early-onset osteoporosis from three unrelated cases and was supported by evidence from functional studies. All three patients harboured heterozygous variants in WNT11 gene.

Three unrelated cases are reported in PMID: 34875064. A four year-old boy harbouring de novo heterozygous loss-of-function variant c.677_678dupGG (p.Leu227Glyfs*22) was reported with low BMD, osteopenia and several fractures.

A 51 year-old woman and her 69 year-old mother were identified with a heterozygous missense variant c.217G>A (p.Ala73Thr). The woman was reported with bone fragility, several fractures, osteoarthritis and osteoporosis, while her mother also had several osteoporotic fractures.

A 61 year-old woman that was reported with lumbar spine osteoarthritis had several fractures since 55 years of age was identified with a heterozygous missense variant c.865G>A (p.Val289Met).

This was also supported by results from functional studies, where cell lines with the loss-of-function variant generated by CRISPR-Cas9 showed reduced cell proliferation and osteoblast differentiation in comparison to wild-type. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells.

This gene has not yet been reported with any phenotypes either in OMIM or in G2P.
Sources: Literature
Osteogenesis imperfecta v3.7 WNT11 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: WNT11.
Osteogenesis imperfecta v3.7 WNT11 Achchuthan Shanmugasundram Classified gene: WNT11 as Amber List (moderate evidence)
Osteogenesis imperfecta v3.7 WNT11 Achchuthan Shanmugasundram Gene: wnt11 has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v3.6 WNT11 Achchuthan Shanmugasundram gene: WNT11 was added
gene: WNT11 was added to Osteogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: WNT11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WNT11 were set to 34875064
Phenotypes for gene: WNT11 were set to osteoporosis, MONDO:0005298; osteoarthritis, MONDO:0005178; recurrent fractures
Review for gene: WNT11 was set to GREEN
Added comment: Comment on gene classification: The rating of this gene can be added as green as this gene has been implicated in early-onset osteoporosis from three unrelated cases and was supported by evidence from functional studies. All three patients harboured heterozygous variants in WNT11 gene.

Three unrelated cases are reported in PMID: 34875064. A four year-old boy harbouring de novo heterozygous loss-of-function variant c.677_678dupGG (p.Leu227Glyfs*22) was reported with low BMD, osteopenia and several fractures.

A 51 year-old woman and her 69 year-old mother were identified with a heterozygous missense variant c.217G>A (p.Ala73Thr). The woman was reported with bone fragility, several fractures, osteoarthritis and osteoporosis, while her mother also had several osteoporotic fractures.

A 61 year-old woman that was reported with lumbar spine osteoarthritis had several fractures since 55 years of age was identified with a heterozygous missense variant c.865G>A (p.Val289Met).

This was also supported by results from functional studies, where cell lines with the loss-of-function variant generated by CRISPR-Cas9 showed reduced cell proliferation and osteoblast differentiation in comparison to wild-type. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells.
Sources: Literature
Osteogenesis imperfecta v3.5 P4HB Eleanor Williams Tag Q2_22_MOI was removed from gene: P4HB.
Osteogenesis imperfecta v3.5 SGMS2 Eleanor Williams Tag Q3_21_rating was removed from gene: SGMS2.
Osteogenesis imperfecta v3.5 DSPP Eleanor Williams Tag Q3_22_rating was removed from gene: DSPP.
Tag Q3_22_expert_review was removed from gene: DSPP.
Osteogenesis imperfecta v3.5 COPB2 Eleanor Williams Tag Q3_21_rating was removed from gene: COPB2.
Osteogenesis imperfecta v3.5 P4HB Eleanor Williams commented on gene: P4HB: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Osteogenesis imperfecta v3.5 SGMS2 Eleanor Williams edited their review of gene: SGMS2: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The reviewers note that the associated phenotype appears variable, and that R104 Skeletal Dysplasia panel looks a better fit for this gene.; Changed rating: AMBER
Osteogenesis imperfecta v3.5 DSPP Eleanor Williams edited their review of gene: DSPP: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Osteogenesis imperfecta v3.5 COPB2 Eleanor Williams commented on gene: COPB2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Osteogenesis imperfecta v3.4 P4HB Eleanor Williams Mode of inheritance for gene P4HB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis imperfecta v3.4 DSPP Eleanor Williams Source Expert Review Red was added to DSPP.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Osteogenesis imperfecta v3.4 COPB2 Eleanor Williams Source Expert Review Green was added to COPB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Osteogenesis imperfecta v3.3 SHOX Arina Puzriakova Mode of inheritance for gene: SHOX was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Osteogenesis imperfecta v3.2 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from Short stature, idiopathic familial, 300582; Leri-Weill dyschondrosteosis, 127300; Langer mesomelic dysplasia, 249700; Proportionate Short Stature/Small for Gestational Age; Disproportionate Short Stature to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582; Dorsolateral bowed, short radii; Bowing and curving of radius; Radioulnar shortening
Osteogenesis imperfecta v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Osteogenesis imperfecta v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Osteogenesis imperfecta v2.48 DSPP Eleanor Williams commented on gene: DSPP: Updating tags to be Q3_22_expert_review and Q3_22_rating so that gene is included in the next GMS report (Oct 2022)
Osteogenesis imperfecta v2.48 DSPP Eleanor Williams Tag Q3_21_expert_review was removed from gene: DSPP.
Tag Q3_22_rating tag was added to gene: DSPP.
Tag Q3_22_expert_review tag was added to gene: DSPP.
Osteogenesis imperfecta v2.48 KDELR2 Arina Puzriakova Phenotypes for gene: KDELR2 were changed from Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms; Osteogenesis imperfecta to Osteogenesis imperfecta, type XXI, OMIM:619131; Increased susceptibility to fractures; Joint hypermobility; Scoliosis; Bowing of the legs and arms
Osteogenesis imperfecta v2.47 COL1A2 Eleanor Williams Added comment: Comment on mode of inheritance: In OMIM this gene is associated with 4 Osteogenesis imperfecta phenotypes, all of which are listed with an autosomal dominant mode of inheritance.

The gene is associated with Ehlers-Danlos syndrome, cardiac valvular type with a autosomal recessive mode of inheritance but this does not appear to affect the bones.

Therefore, monoallelic is the appropriate mode of inheritance for this gene on this panel.
Osteogenesis imperfecta v2.47 COL1A2 Eleanor Williams Mode of inheritance for gene: COL1A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Osteogenesis imperfecta v2.46 MBTPS2 Eleanor Williams Publications for gene: MBTPS2 were set to 27380894
Osteogenesis imperfecta v2.45 P4HB Eleanor Williams Tag Q2_22_MOI tag was added to gene: P4HB.
Osteogenesis imperfecta v2.45 P4HB Eleanor Williams Phenotypes for gene: P4HB were changed from Cole-Carpenter Syndrome; Osteogenesis Imperfecta; Cole Carpenter syndrome to Cole-Carpenter syndrome 1, OMIM:112240; Cole-Carpenter syndrome 1, MONDO:000720
Osteogenesis imperfecta v2.44 P4HB Eleanor Williams Added comment: Comment on mode of inheritance: Cole-Carpenter syndrome 1 is due to heterozygous variants in P4HB and so the mode of inheritance should be changed to monoallelic at the next review.
Osteogenesis imperfecta v2.44 P4HB Eleanor Williams Mode of inheritance for gene: P4HB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Osteogenesis imperfecta v2.43 UNC45A Eleanor Williams Tag Q3_21_rating was removed from gene: UNC45A.
Tag Q3_21_NHS_review was removed from gene: UNC45A.
Osteogenesis imperfecta v2.43 MBTPS2 Eleanor Williams Tag Q3_21_rating was removed from gene: MBTPS2.
Tag Q3_21_NHS_review was removed from gene: MBTPS2.
Tag Q3_21_expert_review was removed from gene: MBTPS2.
Osteogenesis imperfecta v2.43 UNC45A Eleanor Williams commented on gene: UNC45A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Osteogenesis imperfecta v2.43 MBTPS2 Eleanor Williams commented on gene: MBTPS2: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed. It has been agreed that this gene should remain amber at this time.
Osteogenesis imperfecta v2.42 UNC45A Eleanor Williams Source Expert Review Green was added to UNC45A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Osteogenesis imperfecta v2.41 KDELR2 Eleanor Williams Publications for gene: KDELR2 were set to 33053334
Osteogenesis imperfecta v2.40 MESD Eleanor Williams Publications for gene: MESD were set to 31564437
Osteogenesis imperfecta v2.39 MESD Eleanor Williams Tag for-review was removed from gene: MESD.
Osteogenesis imperfecta v2.39 KDELR2 Eleanor Williams Tag for-review was removed from gene: KDELR2.
Osteogenesis imperfecta v2.39 KDELR2 Eleanor Williams commented on gene: KDELR2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Osteogenesis imperfecta v2.39 MESD Eleanor Williams commented on gene: MESD: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Osteogenesis imperfecta v2.38 KDELR2 Eleanor Williams Source Expert Review Green was added to KDELR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Osteogenesis imperfecta v2.38 MESD Eleanor Williams Source Expert Review Green was added to MESD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Osteogenesis imperfecta v2.37 MBTPS2 Michael Oldridge reviewed gene: MBTPS2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 34093655; Phenotypes: OI type XIX OMIM301014; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Osteogenesis imperfecta v2.37 SHOX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SHOX.
Osteogenesis imperfecta v2.37 MBTPS2 Eleanor Williams Tag Q3_21_NHS_review tag was added to gene: MBTPS2.
Osteogenesis imperfecta v2.37 COPB2 Eleanor Williams Classified gene: COPB2 as Amber List (moderate evidence)
Osteogenesis imperfecta v2.37 COPB2 Eleanor Williams Added comment: Comment on list classification: Leaving as amber for now, but there are 2 cases with fractures and 4 with osteopaenia, plus a mouse model with low bone mass, so sufficient to rate green after then next GMS review.
Osteogenesis imperfecta v2.37 COPB2 Eleanor Williams Gene: copb2 has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v2.36 COPB2 Eleanor Williams Tag watchlist_moi tag was added to gene: COPB2.
Osteogenesis imperfecta v2.36 TAPT1 Eleanor Williams Classified gene: TAPT1 as Green List (high evidence)
Osteogenesis imperfecta v2.36 TAPT1 Eleanor Williams Added comment: Comment on list classification: Leaving rating as green; 2 cases reported, supportive zebrafish data and green review by NHS expert.
Osteogenesis imperfecta v2.36 TAPT1 Eleanor Williams Gene: tapt1 has been classified as Green List (High Evidence).
Osteogenesis imperfecta v2.35 TAPT1 Eleanor Williams commented on gene: TAPT1: Only 2 cases reported but PMID: 26365339 - Symoens et al 2015 - also report that knock-down of zebrafish tapt1b resulted in severe malformations of the craniofacial skeleton and delayed ossification.

PMID: 17151244 - Howell et al 2007 - also reports a skeletal phenotype in a mouse with a homozygous mutation in Tapt1, primarily posterior-to-anterior transformations of the vertebral column midsection.
Osteogenesis imperfecta v2.35 DSPP Eleanor Williams Tag Q3_21_expert_review tag was added to gene: DSPP.
Osteogenesis imperfecta v2.35 DSPP Eleanor Williams commented on gene: DSPP: Conflicting reviews so tagging for GMS review.
Osteogenesis imperfecta v2.35 SGMS2 Eleanor Williams Classified gene: SGMS2 as Amber List (moderate evidence)
Osteogenesis imperfecta v2.35 SGMS2 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber but with a recommendation for green rating following GMS review. 8 cases reported with 3 different variants.
Osteogenesis imperfecta v2.35 SGMS2 Eleanor Williams Gene: sgms2 has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v2.34 SGMS2 Eleanor Williams Tag Q3_21_rating tag was added to gene: SGMS2.
Osteogenesis imperfecta v2.34 SGMS2 Eleanor Williams Phenotypes for gene: SGMS2 were changed from Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550 to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia, OMIM:126550; calvarial doughnut lesions-bone fragility syndrome, MONDO:0007470
Osteogenesis imperfecta v2.33 SGMS2 Eleanor Williams reviewed gene: SGMS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30779713, 32028018; Phenotypes: Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia, OMIM:126550, calvarial doughnut lesions-bone fragility syndrome, MONDO:0007470; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Osteogenesis imperfecta v2.33 COPB2 Eleanor Williams Added comment: Comment on mode of inheritance: Left as monoallelic for now as only 1 biallelic case reported.
Osteogenesis imperfecta v2.33 COPB2 Eleanor Williams Mode of inheritance for gene: COPB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis imperfecta v2.32 SUCO Eleanor Williams Phenotypes for gene: SUCO were changed from Osteogenesis imperfecta; skeletal dysplasia; osteopenia to Osteogenesis imperfecta, MONDO:0019019; skeletal dysplasia, HP:0002652; osteopenia
Osteogenesis imperfecta v2.31 SUCO Eleanor Williams Phenotypes for gene: SUCO were changed from Osteogenesis imperfecta to Osteogenesis imperfecta; skeletal dysplasia; osteopenia
Osteogenesis imperfecta v2.30 SUCO Eleanor Williams Classified gene: SUCO as Amber List (moderate evidence)
Osteogenesis imperfecta v2.30 SUCO Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. 1 case plus supportive mouse model.
Osteogenesis imperfecta v2.30 SUCO Eleanor Williams Gene: suco has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v2.29 SUCO Eleanor Williams reviewed gene: SUCO: Rating: AMBER; Mode of pathogenicity: None; Publications: 29620724, 20440000; Phenotypes: skeletal dysplasia, osteopenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v2.29 COPB2 Eleanor Williams changed review comment from: As Zornitza Stark reports, PMID: 34450031 - Marom et al 2021 describes 6 individuals from 5 families. In 4 families loss of function heterozygous variants in COPB2 were found. In the 5th family, two affected siblings were found to have a homozygous variant in COPB2. Osteopenia was noted in 4/5 families (5th unknown) and fractures in 2/5. Developmental delay was observed in all 6 individuals. Severe intellectual disability, seizures and microcephaly was noted in the siblings with the homozygous variants. Copb2þ +/-mice exhibit low bone mass; to: As Zornitza Stark reports, PMID: 34450031 - Marom et al 2021 describes 6 individuals from 5 families. In 4 families loss of function heterozygous variants in COPB2 were found. In the 5th family, two affected siblings were found to have a homozygous variant in COPB2. Osteopenia was noted in 4/5 families (5th unknown) and fractures in 2/5. Developmental delay was observed in all 6 individuals. Severe intellectual disability, seizures and microcephaly was noted in the siblings with the homozygous variants. Copb2 +/-mice exhibit low bone mass.

PMID: 29036432 - original report of microcephaly in the two siblings with the COPB2 homozygous variant.
Osteogenesis imperfecta v2.29 COPB2 Eleanor Williams Publications for gene: COPB2 were set to 34450031
Osteogenesis imperfecta v2.28 COPB2 Eleanor Williams Phenotypes for gene: COPB2 were changed from juvenile osteoporosis to juvenile osteoporosis; Osteopenia; Osteoporosis; recurrent fractures
Osteogenesis imperfecta v2.27 COPB2 Eleanor Williams Publications for gene: COPB2 were set to Marom et al 2018 ASBMR: COPB2 Loss of Function Leads to Disrupted Collagen Trafficking and Juvenile Osteoporosis
Osteogenesis imperfecta v2.26 COPB2 Eleanor Williams Tag Q3_21_rating tag was added to gene: COPB2.
Osteogenesis imperfecta v2.26 COPB2 Eleanor Williams edited their review of gene: COPB2: Added comment: As Zornitza Stark reports, PMID: 34450031 - Marom et al 2021 describes 6 individuals from 5 families. In 4 families loss of function heterozygous variants in COPB2 were found. In the 5th family, two affected siblings were found to have a homozygous variant in COPB2. Osteopenia was noted in 4/5 families (5th unknown) and fractures in 2/5. Developmental delay was observed in all 6 individuals. Severe intellectual disability, seizures and microcephaly was noted in the siblings with the homozygous variants. Copb2þ +/-mice exhibit low bone mass; Changed rating: GREEN; Changed publications to: 34450031; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Osteogenesis imperfecta v2.26 MESD Eleanor Williams commented on gene: MESD: Further green review from NHS clinician, but already tagged for green rating in next GMS review.
Osteogenesis imperfecta v2.26 FAM46A Eleanor Williams commented on gene: FAM46A: Further green review by Meena Balasubramanian, so keeping green rating.
Osteogenesis imperfecta v2.26 FAM46A Eleanor Williams Phenotypes for gene: FAM46A were changed from Osteogenesis imperfecta, type XVIII, OMIM:617952 to Osteogenesis imperfecta, type XVIII, OMIM:617952; osteogenesis imperfecta, type 18, MONDO:0044329
Osteogenesis imperfecta v2.25 MBTPS2 Eleanor Williams Classified gene: MBTPS2 as Amber List (moderate evidence)
Osteogenesis imperfecta v2.25 MBTPS2 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. Only 2 cases reported in literature so waiting for further GMS feedback on the rating of this gene.
Osteogenesis imperfecta v2.25 MBTPS2 Eleanor Williams Gene: mbtps2 has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v2.24 MBTPS2 Eleanor Williams changed review comment from: Associated with Osteogenesis imperfecta, type XIX #301014 (AR) in OMIM.

PMID: 27380894 - Lindert et al 2016 - report two independent OI pedigrees (Thai and German) without symptoms of any dermatological condition previously associated with variants in this gene(ichthyosis follicularis, atrichia, and photophobia (IFAP); BRESEK/BRESHECK syndrome; and keratosis follicularis spinulosa decalvans (KFSD)). In both families missense mutations were identified which was in or near the S2P NPDG motif vital for metal ion coordination. All those affected were male. Mutant S2P protein was found to be stable but cleavage or activation of S2P substrates OASIS and ATF6, respectively, was impaired, consistent with reduced proband collagen secretion.

A search of PubMed find no further cases.; to: Associated with Osteogenesis imperfecta, type XIX #301014 (AR) in OMIM.

PMID: 27380894 - Lindert et al 2016 - report two independent OI pedigrees (Thai and German) without symptoms of any dermatological condition previously associated with variants in this gene(ichthyosis follicularis, atrichia, and photophobia (IFAP); BRESEK/BRESHECK syndrome; and keratosis follicularis spinulosa decalvans (KFSD)). In both families missense mutations were identified which was in or near the S2P NPDG motif vital for metal ion coordination. All those affected were male. Mutant S2P protein was found to be stable but cleavage or activation of S2P substrates OASIS and ATF6, respectively, was impaired, consistent with reduced proband collagen secretion.

A search of PubMed finds no further cases.
Osteogenesis imperfecta v2.24 MBTPS2 Eleanor Williams Phenotypes for gene: MBTPS2 were changed from Osteogenesis imperfecta, type XIX, MIM# 301014 to Osteogenesis imperfecta, type XIX, OMIM:301014; osteogenesis imperfecta, type 19, MONDO:0049223
Osteogenesis imperfecta v2.23 MBTPS2 Eleanor Williams Tag Q3_21_rating tag was added to gene: MBTPS2.
Tag Q3_21_expert_review tag was added to gene: MBTPS2.
Osteogenesis imperfecta v2.23 MBTPS2 Eleanor Williams reviewed gene: MBTPS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27380894; Phenotypes: Osteogenesis imperfecta, type XIX, OMIM:301014; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Osteogenesis imperfecta v2.23 COPB2 Zornitza Stark reviewed gene: COPB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34450031; Phenotypes: Osteoporosis, recurrent fractures and developmental delay; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Osteogenesis imperfecta v2.23 SUCO Zornitza Stark gene: SUCO was added
gene: SUCO was added to Osteogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: SUCO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUCO were set to 29620724; 20440000
Phenotypes for gene: SUCO were set to Osteogenesis imperfecta
Review for gene: SUCO was set to AMBER
Added comment: A single case with diffuse osteopenia, multiple fractures with limb deformities, and short long bones, with biallelic variants (a missense and a splice site variant). Also, a null mouse model with acute onset skeletal defects that include impaired bone formation and spontaneous fractures.
Sources: Literature
Osteogenesis imperfecta v2.23 KDELR2 Meena Balasubramanian reviewed gene: KDELR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33964184, 33053334; Phenotypes: Ostoegenesis Imperfecta, Fractures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v2.23 MESD Meena Balasubramanian reviewed gene: MESD: Rating: GREEN; Mode of pathogenicity: None; Publications: 33596325, 31564437; Phenotypes: Ostoegenesis Imperfecta, Fractures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v2.23 FAM46A Meena Balasubramanian reviewed gene: FAM46A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29358272; Phenotypes: Ostoegenesis Imperfecta, Fractures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v2.23 MBTPS2 Meena Balasubramanian reviewed gene: MBTPS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27380894; Phenotypes: Ostoegenesis Imperfecta, Fractures; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Osteogenesis imperfecta v2.23 SPARC Arina Puzriakova Phenotypes for gene: SPARC were changed from Osteogenesis Imperfecta, Type XVII; Osteogenesis Imperfecta to Osteogenesis imperfecta, type XVII, OMIM:616507
Osteogenesis imperfecta v2.22 SPARC Arina Puzriakova Publications for gene: SPARC were set to 26027498
Osteogenesis imperfecta v2.21 UNC45A Eleanor Williams Tag Q3_21_NHS_review tag was added to gene: UNC45A.
Osteogenesis imperfecta v2.21 UNC45A Eleanor Williams Phenotypes for gene: UNC45A were changed from cholestasis; congenital diarrhea; impaired hearing; bone fragility to Osteootohepatoenteric syndrome, OMIM:619377
Osteogenesis imperfecta v2.20 UNC45A Eleanor Williams Classified gene: UNC45A as Amber List (moderate evidence)
Osteogenesis imperfecta v2.20 UNC45A Eleanor Williams Gene: unc45a has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v2.19 UNC45A Eleanor Williams Classified gene: UNC45A as No list
Osteogenesis imperfecta v2.19 UNC45A Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, with recommendation for green rating following GMS review. 2 unrelated families with bone fragility and biallelic variants in this gene reported in the literature, plus another case reported by an NHS laboratory.
Osteogenesis imperfecta v2.19 UNC45A Eleanor Williams Gene: unc45a has been removed from the panel.
Osteogenesis imperfecta v2.18 UNC45A Eleanor Williams Tag Q3_21_rating tag was added to gene: UNC45A.
Osteogenesis imperfecta v2.18 UNC45A Eleanor Williams reviewed gene: UNC45A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29429573; Phenotypes: Osteootohepatoenteric syndrome, OMIM:619377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v2.18 WNT1 Ivone Leong Phenotypes for gene: WNT1 were changed from Osteogenesis imperfecta, type XV, 615220; {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, 615221 to Osteogenesis imperfecta, type XV, OMIM:615220; {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, OMIM:615221
Osteogenesis imperfecta v2.17 WNT1 Ivone Leong Publications for gene: WNT1 were set to 23434763; 2349931
Osteogenesis imperfecta v2.16 WNT1 Ivone Leong Phenotypes for gene: WNT1 were changed from Osteogenesis imperfecta, type XV, 615220; {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, 615221; osteogenesis imperfecta to Osteogenesis imperfecta, type XV, 615220; {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, 615221
Osteogenesis imperfecta v2.15 WNT1 Ivone Leong Publications for gene: WNT1 were set to PMID: 23434763; 2349931
Osteogenesis imperfecta v2.14 FAM46A Arina Puzriakova Phenotypes for gene: FAM46A were changed from osteogenesis imperfecta to Osteogenesis imperfecta, type XVIII, OMIM:617952
Osteogenesis imperfecta v2.13 WRN Arina Puzriakova Tag curated_removed tag was added to gene: WRN.
Osteogenesis imperfecta v2.13 WNT5A Arina Puzriakova Tag curated_removed tag was added to gene: WNT5A.
Osteogenesis imperfecta v2.13 WDR35 Arina Puzriakova Tag curated_removed tag was added to gene: WDR35.
Osteogenesis imperfecta v2.13 TRPV4 Arina Puzriakova Tag curated_removed tag was added to gene: TRPV4.
Osteogenesis imperfecta v2.13 TRPS1 Arina Puzriakova Tag curated_removed tag was added to gene: TRPS1.
Osteogenesis imperfecta v2.13 TRIP11 Arina Puzriakova Tag curated_removed tag was added to gene: TRIP11.
Osteogenesis imperfecta v2.13 TRIM37 Arina Puzriakova Tag curated_removed tag was added to gene: TRIM37.
Osteogenesis imperfecta v2.13 THRB Arina Puzriakova Tag curated_removed tag was added to gene: THRB.
Osteogenesis imperfecta v2.13 TCTN3 Arina Puzriakova Tag curated_removed tag was added to gene: TCTN3.
Osteogenesis imperfecta v2.13 TBCE Arina Puzriakova Tag curated_removed tag was added to gene: TBCE.
Osteogenesis imperfecta v2.13 SULF1 Arina Puzriakova Tag curated_removed tag was added to gene: SULF1.
Osteogenesis imperfecta v2.13 STAT5B Arina Puzriakova Tag curated_removed tag was added to gene: STAT5B.
Osteogenesis imperfecta v2.13 SRCAP Arina Puzriakova Tag curated_removed tag was added to gene: SRCAP.
Osteogenesis imperfecta v2.13 SOX9 Arina Puzriakova Tag curated_removed tag was added to gene: SOX9.
Osteogenesis imperfecta v2.13 SOX3 Arina Puzriakova Tag curated_removed tag was added to gene: SOX3.
Osteogenesis imperfecta v2.13 SOX2 Arina Puzriakova Tag curated_removed tag was added to gene: SOX2.
Osteogenesis imperfecta v2.13 SOS1 Arina Puzriakova Tag curated_removed tag was added to gene: SOS1.
Osteogenesis imperfecta v2.13 SMC3 Arina Puzriakova Tag curated_removed tag was added to gene: SMC3.
Osteogenesis imperfecta v2.13 SMC1A Arina Puzriakova Tag curated_removed tag was added to gene: SMC1A.
Osteogenesis imperfecta v2.13 SMARCAL1 Arina Puzriakova Tag curated_removed tag was added to gene: SMARCAL1.
Osteogenesis imperfecta v2.13 SLC39A13 Arina Puzriakova Tag curated_removed tag was added to gene: SLC39A13.
Osteogenesis imperfecta v2.13 SLC35D1 Arina Puzriakova Tag curated_removed tag was added to gene: SLC35D1.
Osteogenesis imperfecta v2.13 SLC26A2 Arina Puzriakova Tag curated_removed tag was added to gene: SLC26A2.
Osteogenesis imperfecta v2.13 SHOX2 Arina Puzriakova Tag curated_removed tag was added to gene: SHOX2.
Osteogenesis imperfecta v2.13 SH3PXD2B Arina Puzriakova Tag curated_removed tag was added to gene: SH3PXD2B.
Osteogenesis imperfecta v2.13 RUNX2 Arina Puzriakova Tag curated_removed tag was added to gene: RUNX2.
Osteogenesis imperfecta v2.13 RPS6KA3 Arina Puzriakova Tag curated_removed tag was added to gene: RPS6KA3.
Osteogenesis imperfecta v2.13 ROR2 Arina Puzriakova Tag curated_removed tag was added to gene: ROR2.
Osteogenesis imperfecta v2.13 RAF1 Arina Puzriakova Tag curated_removed tag was added to gene: RAF1.
Osteogenesis imperfecta v2.13 PTPN11 Arina Puzriakova Tag curated_removed tag was added to gene: PTPN11.
Osteogenesis imperfecta v2.13 PTH1R Arina Puzriakova Tag curated_removed tag was added to gene: PTH1R.
Osteogenesis imperfecta v2.13 PROP1 Arina Puzriakova Tag curated_removed tag was added to gene: PROP1.
Osteogenesis imperfecta v2.13 PRKAR1A Arina Puzriakova Tag curated_removed tag was added to gene: PRKAR1A.
Osteogenesis imperfecta v2.13 POU1F1 Arina Puzriakova Tag curated_removed tag was added to gene: POU1F1.
Osteogenesis imperfecta v2.13 PITX2 Arina Puzriakova Tag curated_removed tag was added to gene: PITX2.
Osteogenesis imperfecta v2.13 PCNT Arina Puzriakova Tag curated_removed tag was added to gene: PCNT.
Osteogenesis imperfecta v2.13 PAPSS2 Arina Puzriakova Tag curated_removed tag was added to gene: PAPSS2.
Osteogenesis imperfecta v2.13 OBSL1 Arina Puzriakova Tag curated_removed tag was added to gene: OBSL1.
Osteogenesis imperfecta v2.13 NPR2 Arina Puzriakova Tag curated_removed tag was added to gene: NPR2.
Osteogenesis imperfecta v2.13 NKX3-2 Arina Puzriakova Tag curated_removed tag was added to gene: NKX3-2.
Osteogenesis imperfecta v2.13 NIPBL Arina Puzriakova Tag curated_removed tag was added to gene: NIPBL.
Osteogenesis imperfecta v2.13 NEK1 Arina Puzriakova Tag curated_removed tag was added to gene: NEK1.
Osteogenesis imperfecta v2.13 NBN Arina Puzriakova Tag curated_removed tag was added to gene: NBN.
Osteogenesis imperfecta v2.13 MMP9 Arina Puzriakova Tag curated_removed tag was added to gene: MMP9.
Osteogenesis imperfecta v2.13 MMP13 Arina Puzriakova Tag curated_removed tag was added to gene: MMP13.
Osteogenesis imperfecta v2.13 LIFR Arina Puzriakova Tag curated_removed tag was added to gene: LIFR.
Osteogenesis imperfecta v2.13 LHX3 Arina Puzriakova Tag curated_removed tag was added to gene: LHX3.
Osteogenesis imperfecta v2.13 KRAS Arina Puzriakova Tag curated_removed tag was added to gene: KRAS.
Osteogenesis imperfecta v2.13 KMT2D Arina Puzriakova Tag curated_removed tag was added to gene: KMT2D.
Osteogenesis imperfecta v2.13 KIF22 Arina Puzriakova Tag curated_removed tag was added to gene: KIF22.
Osteogenesis imperfecta v2.13 KDM6A Arina Puzriakova Tag curated_removed tag was added to gene: KDM6A.
Osteogenesis imperfecta v2.13 INSR Arina Puzriakova Tag curated_removed tag was added to gene: INSR.
Osteogenesis imperfecta v2.13 IHH Arina Puzriakova Tag curated_removed tag was added to gene: IHH.
Osteogenesis imperfecta v2.13 IGF1R Arina Puzriakova Tag curated_removed tag was added to gene: IGF1R.
Osteogenesis imperfecta v2.13 IGF1 Arina Puzriakova Tag curated_removed tag was added to gene: IGF1.
Osteogenesis imperfecta v2.13 IFT80 Arina Puzriakova Tag curated_removed tag was added to gene: IFT80.
Osteogenesis imperfecta v2.13 IFT140 Arina Puzriakova Tag curated_removed tag was added to gene: IFT140.
Osteogenesis imperfecta v2.13 IFT122 Arina Puzriakova Tag curated_removed tag was added to gene: IFT122.
Osteogenesis imperfecta v2.13 ICK Arina Puzriakova Tag curated_removed tag was added to gene: ICK.
Osteogenesis imperfecta v2.13 HSPG2 Arina Puzriakova Tag curated_removed tag was added to gene: HSPG2.
Osteogenesis imperfecta v2.13 HESX1 Arina Puzriakova Tag curated_removed tag was added to gene: HESX1.
Osteogenesis imperfecta v2.13 GPC6 Arina Puzriakova Tag curated_removed tag was added to gene: GPC6.
Osteogenesis imperfecta v2.13 GLI3 Arina Puzriakova Tag curated_removed tag was added to gene: GLI3.
Osteogenesis imperfecta v2.13 GLI2 Arina Puzriakova Tag curated_removed tag was added to gene: GLI2.
Osteogenesis imperfecta v2.13 GHSR Arina Puzriakova Tag curated_removed tag was added to gene: GHSR.
Osteogenesis imperfecta v2.13 GHRHR Arina Puzriakova Tag curated_removed tag was added to gene: GHRHR.
Osteogenesis imperfecta v2.13 GH1 Arina Puzriakova Tag curated_removed tag was added to gene: GH1.
Osteogenesis imperfecta v2.13 GDF5 Arina Puzriakova Tag curated_removed tag was added to gene: GDF5.
Osteogenesis imperfecta v2.13 FLNB Arina Puzriakova Tag curated_removed tag was added to gene: FLNB.
Osteogenesis imperfecta v2.13 FLNA Arina Puzriakova Tag curated_removed tag was added to gene: FLNA.
Osteogenesis imperfecta v2.13 FGFR3 Arina Puzriakova Tag curated_removed tag was added to gene: FGFR3.
Osteogenesis imperfecta v2.13 FGFR2 Arina Puzriakova Tag curated_removed tag was added to gene: FGFR2.
Osteogenesis imperfecta v2.13 FGFR1 Arina Puzriakova Tag curated_removed tag was added to gene: FGFR1.
Osteogenesis imperfecta v2.13 FGD1 Arina Puzriakova Tag curated_removed tag was added to gene: FGD1.
Osteogenesis imperfecta v2.13 FBN1 Arina Puzriakova Tag curated_removed tag was added to gene: FBN1.
Osteogenesis imperfecta v2.13 FAM20C Arina Puzriakova Tag curated_removed tag was added to gene: FAM20C.
Osteogenesis imperfecta v2.13 EXT2 Arina Puzriakova Tag curated_removed tag was added to gene: EXT2.
Osteogenesis imperfecta v2.13 EXT1 Arina Puzriakova Tag curated_removed tag was added to gene: EXT1.
Osteogenesis imperfecta v2.13 EVC2 Arina Puzriakova Tag curated_removed tag was added to gene: EVC2.
Osteogenesis imperfecta v2.13 EVC Arina Puzriakova Tag curated_removed tag was added to gene: EVC.
Osteogenesis imperfecta v2.13 ERCC8 Arina Puzriakova Tag curated_removed tag was added to gene: ERCC8.
Osteogenesis imperfecta v2.13 ERCC6 Arina Puzriakova Tag curated_removed tag was added to gene: ERCC6.
Osteogenesis imperfecta v2.13 EP300 Arina Puzriakova Tag curated_removed tag was added to gene: EP300.
Osteogenesis imperfecta v2.13 EIF2AK3 Arina Puzriakova Tag curated_removed tag was added to gene: EIF2AK3.
Osteogenesis imperfecta v2.13 DYNC2H1 Arina Puzriakova Tag curated_removed tag was added to gene: DYNC2H1.
Osteogenesis imperfecta v2.13 DYM Arina Puzriakova Tag curated_removed tag was added to gene: DYM.
Osteogenesis imperfecta v2.13 DHCR7 Arina Puzriakova Tag curated_removed tag was added to gene: DHCR7.
Osteogenesis imperfecta v2.13 DHCR24 Arina Puzriakova Tag curated_removed tag was added to gene: DHCR24.
Osteogenesis imperfecta v2.13 DDR2 Arina Puzriakova Tag curated_removed tag was added to gene: DDR2.
Osteogenesis imperfecta v2.13 CUL7 Arina Puzriakova Tag curated_removed tag was added to gene: CUL7.
Osteogenesis imperfecta v2.13 CTSK Arina Puzriakova Tag curated_removed tag was added to gene: CTSK.
Osteogenesis imperfecta v2.13 COMP Arina Puzriakova Tag curated_removed tag was added to gene: COMP.
Osteogenesis imperfecta v2.13 COL9A3 Arina Puzriakova Tag curated_removed tag was added to gene: COL9A3.
Osteogenesis imperfecta v2.13 COL9A2 Arina Puzriakova Tag curated_removed tag was added to gene: COL9A2.
Osteogenesis imperfecta v2.13 COL9A1 Arina Puzriakova Tag curated_removed tag was added to gene: COL9A1.
Osteogenesis imperfecta v2.13 CHST3 Arina Puzriakova Tag curated_removed tag was added to gene: CHST3.
Osteogenesis imperfecta v2.13 CHST14 Arina Puzriakova Tag curated_removed tag was added to gene: CHST14.
Osteogenesis imperfecta v2.13 CDKN1C Arina Puzriakova Tag curated_removed tag was added to gene: CDKN1C.
Osteogenesis imperfecta v2.13 CANT1 Arina Puzriakova Tag curated_removed tag was added to gene: CANT1.
Osteogenesis imperfecta v2.13 BTK Arina Puzriakova Tag curated_removed tag was added to gene: BTK.
Osteogenesis imperfecta v2.13 BMPR1B Arina Puzriakova Tag curated_removed tag was added to gene: BMPR1B.
Osteogenesis imperfecta v2.13 BLM Arina Puzriakova Tag curated_removed tag was added to gene: BLM.
Osteogenesis imperfecta v2.13 ATRX Arina Puzriakova Tag curated_removed tag was added to gene: ATRX.
Osteogenesis imperfecta v2.13 ACP5 Arina Puzriakova Tag curated_removed tag was added to gene: ACP5.
Osteogenesis imperfecta v2.13 UNC45A Julia Baptista reviewed gene: UNC45A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29429573; Phenotypes: cholestasis, diarrhea, bone fragility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Osteogenesis imperfecta v2.13 MESD Arina Puzriakova Phenotypes for gene: MESD were changed from Osteogenesis imperfecta, type XX, 618644 to Osteogenesis imperfecta, type XX, OMIM:618644; Osteogenesis imperfecta, type 20, MONDO:0032846
Osteogenesis imperfecta v2.12 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Disproportionate Short Stature to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Osteogenesis imperfecta v2.11 TMEM38B Arina Puzriakova Phenotypes for gene: TMEM38B were changed from Osteogenesis imperfecta, type XIV, 615066; osteogenesis imperfecta to Osteogenesis imperfecta, type XIV, OMIM:615066; Osteogenesis imperfecta type 14, MONDO:0014029
Osteogenesis imperfecta v2.10 KDELR2 Eleanor Williams Publications for gene: KDELR2 were set to PMID: 33053334
Osteogenesis imperfecta v2.9 KDELR2 Eleanor Williams Tag for-review tag was added to gene: KDELR2.
Osteogenesis imperfecta v2.9 KDELR2 Eleanor Williams Phenotypes for gene: KDELR2 were changed from Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms; Osteogenesis imperfecta
Osteogenesis imperfecta v2.8 KDELR2 Eleanor Williams Classified gene: KDELR2 as Amber List (moderate evidence)
Osteogenesis imperfecta v2.8 KDELR2 Eleanor Williams Added comment: Comment on list classification: Changing the status from grey to amber, but with a recommendation for a green rating following GMS review.
Osteogenesis imperfecta v2.8 KDELR2 Eleanor Williams Gene: kdelr2 has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v2.7 KDELR2 Eleanor Williams reviewed gene: KDELR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33053334; Phenotypes: Osteogenesis imperfecta; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v2.7 KDELR2 Dmitrijs Rots gene: KDELR2 was added
gene: KDELR2 was added to Osteogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to PMID: 33053334
Phenotypes for gene: KDELR2 were set to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms
Penetrance for gene: KDELR2 were set to Complete
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies reported in PMID: 33053334
Sources: Literature
Osteogenesis imperfecta v2.7 MESD Arina Puzriakova Classified gene: MESD as Amber List (moderate evidence)
Osteogenesis imperfecta v2.7 MESD Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.
Osteogenesis imperfecta v2.7 MESD Arina Puzriakova Gene: mesd has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v2.6 MBTPS2 Zornitza Stark gene: MBTPS2 was added
gene: MBTPS2 was added to Osteogenesis imperfecta. Sources: Expert list
Mode of inheritance for gene: MBTPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MBTPS2 were set to 27380894
Phenotypes for gene: MBTPS2 were set to Osteogenesis imperfecta, type XIX, MIM# 301014
Review for gene: MBTPS2 was set to AMBER
Added comment: Two unrelated families reported with multiple male affected individuals.
Sources: Expert list
Osteogenesis imperfecta v2.6 UNC45A Zornitza Stark gene: UNC45A was added
gene: UNC45A was added to Osteogenesis imperfecta. Sources: Expert list
Mode of inheritance for gene: UNC45A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC45A were set to 29429573
Phenotypes for gene: UNC45A were set to cholestasis; congenital diarrhea; impaired hearing; bone fragility
Review for gene: UNC45A was set to AMBER
Added comment: Bone fragility is present in 3 cases from two families and is not present in another case with biallelic variants. In vitro functional assays suggest loss-of-function mechanism of disease. In vivo zebrafish assays demonstrate defects in gut development and bone fragility doesn't appear to be assessed. Emerging gene-disease association, uncertain if bone fragility is a consistent/prominent feature of the phenotype yet.
Sources: Expert list
Osteogenesis imperfecta v2.6 SGMS2 Zornitza Stark gene: SGMS2 was added
gene: SGMS2 was added to Osteogenesis imperfecta. Sources: Expert list
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Review for gene: SGMS2 was set to GREEN
gene: SGMS2 was marked as current diagnostic
Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments.
2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum.
Sources: Expert list
Osteogenesis imperfecta v2.6 DSPP Zornitza Stark reviewed gene: DSPP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dentinogenesis imperfecta 125490; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis imperfecta v2.6 MESD Eleanor Williams Tag for-review tag was added to gene: MESD.
Osteogenesis imperfecta v2.6 MESD Eleanor Williams changed review comment from: Gene suggested by Alistair Pagnamenta.

Associated with Osteogenesis imperfecta, type XX, #618644 (AR) in OMIM.

PMID: 31564437 Moosa et al 2019. Report 5 independent consanguineous families with a progressively deforming type of OI. Using WES and prioritising homozygous variants, they found all patients were homozygous for a mutation in the third and final exon of MESD. Parents were heterozygous. Variants were not common polymorphisms. 4 different truncation or frameshift variants were found. In mice, homozygous loss-of-function Mesd mutations cause embryonic lethality during gastrulation (PubMed: 11247670). In functional studies the MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking.
Sources: Literature; to: Gene suggested by Alistair Pagnamenta.

Associated with Osteogenesis imperfecta, type XX, #618644 (AR) in OMIM.

PMID: 31564437 Moosa et al 2019. Report 5 independent consanguineous families with a progressively deforming type of OI. Using WES and prioritising homozygous variants, they found all patients were homozygous for a mutation in the third and final exon of MESD. Parents were heterozygous. Variants were not common polymorphisms. 4 different truncation or frameshift variants were found. In mice, homozygous loss-of-function Mesd mutations cause embryonic lethality during gastrulation (PubMed: 11247670). In functional studies the MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking.

Alistair Pagnamenta notes that there is a lack of sibling data.
Osteogenesis imperfecta v2.6 MESD Eleanor Williams Classified gene: MESD as Green List (high evidence)
Osteogenesis imperfecta v2.6 MESD Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. More than three families reported, with plausible disease causing variants.
Osteogenesis imperfecta v2.6 MESD Eleanor Williams Gene: mesd has been classified as Green List (High Evidence).
Osteogenesis imperfecta v2.5 MESD Eleanor Williams Phenotypes for gene: MESD were changed from to Osteogenesis imperfecta, type XX, 618644
Osteogenesis imperfecta v2.4 MESD Eleanor Williams gene: MESD was added
gene: MESD was added to Osteogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MESD were set to 31564437
Added comment: Gene suggested by Alistair Pagnamenta.

Associated with Osteogenesis imperfecta, type XX, #618644 (AR) in OMIM.

PMID: 31564437 Moosa et al 2019. Report 5 independent consanguineous families with a progressively deforming type of OI. Using WES and prioritising homozygous variants, they found all patients were homozygous for a mutation in the third and final exon of MESD. Parents were heterozygous. Variants were not common polymorphisms. 4 different truncation or frameshift variants were found. In mice, homozygous loss-of-function Mesd mutations cause embryonic lethality during gastrulation (PubMed: 11247670). In functional studies the MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking.
Sources: Literature
Osteogenesis imperfecta v2.3 TAPT1 Zornitza Stark reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v2.3 Eleanor Williams Panel version has been signed off
Osteogenesis imperfecta v2.2 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Osteogenesis imperfecta v2.0 ICK Eleanor Williams commented on gene: ICK
Osteogenesis imperfecta v2.0 ICK Eleanor Williams Tag new-gene-name tag was added to gene: ICK.
Osteogenesis imperfecta v2.0 Eleanor Williams promoted panel to version 2.0
Osteogenesis imperfecta v1.53 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off
Osteogenesis imperfecta v1.52 Eleanor Williams List of related panels changed from Osteogenesis Imperfecta to Osteogenesis Imperfecta; R102
Osteogenesis imperfecta v1.50 CASR Eleanor Williams Classified gene: CASR as Green List (high evidence)
Osteogenesis imperfecta v1.50 CASR Eleanor Williams Added comment: Comment on list classification: This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.
Osteogenesis imperfecta v1.50 CASR Eleanor Williams Gene: casr has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.49 B4GALT7 Eleanor Williams Classified gene: B4GALT7 as Green List (high evidence)
Osteogenesis imperfecta v1.49 B4GALT7 Eleanor Williams Added comment: Comment on list classification: This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.
Osteogenesis imperfecta v1.49 B4GALT7 Eleanor Williams Gene: b4galt7 has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.48 NUDT6 Eleanor Williams Classified gene: NUDT6 as Amber List (moderate evidence)
Osteogenesis imperfecta v1.48 NUDT6 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to rate this gene amber until there is more evidence for an association.
Osteogenesis imperfecta v1.48 NUDT6 Eleanor Williams Gene: nudt6 has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v1.47 COPB2 Eleanor Williams Classified gene: COPB2 as Amber List (moderate evidence)
Osteogenesis imperfecta v1.47 COPB2 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to make this gene amber.
Osteogenesis imperfecta v1.47 COPB2 Eleanor Williams Gene: copb2 has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v1.46 NBAS Eleanor Williams Classified gene: NBAS as Green List (high evidence)
Osteogenesis imperfecta v1.46 NBAS Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to make this gene green. 2 cases plus functional data.
Osteogenesis imperfecta v1.46 NBAS Eleanor Williams Gene: nbas has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.45 NBAS Eleanor Williams Deleted their comment
Osteogenesis imperfecta v1.45 NBAS Eleanor Williams Classified gene: NBAS as Red List (low evidence)
Osteogenesis imperfecta v1.45 NBAS Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to make this gene green. 2 cases plus functional data.
Osteogenesis imperfecta v1.45 NBAS Eleanor Williams Gene: nbas has been classified as Red List (Low Evidence).
Osteogenesis imperfecta v1.44 NBAS Eleanor Williams Mode of inheritance for gene: NBAS was changed from to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.43 GORAB Eleanor Williams Classified gene: GORAB as Green List (high evidence)
Osteogenesis imperfecta v1.43 GORAB Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to rate this gene green. Sufficient cases.
Osteogenesis imperfecta v1.43 GORAB Eleanor Williams Gene: gorab has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.42 GORAB Eleanor Williams Mode of inheritance for gene: GORAB was changed from to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.41 DSPP Eleanor Williams Classified gene: DSPP as Green List (high evidence)
Osteogenesis imperfecta v1.41 DSPP Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to make this gene green. Sufficient cases.
Osteogenesis imperfecta v1.41 DSPP Eleanor Williams Gene: dspp has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.40 DSPP Eleanor Williams Mode of inheritance for gene: DSPP was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis imperfecta v1.39 CREB3L1 Eleanor Williams Classified gene: CREB3L1 as Green List (high evidence)
Osteogenesis imperfecta v1.39 CREB3L1 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to make this green gene. There is more evidence since the last review.
Osteogenesis imperfecta v1.39 CREB3L1 Eleanor Williams Gene: creb3l1 has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.38 B4GALT7 Eleanor Williams Mode of inheritance for gene: B4GALT7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.37 CASR Eleanor Williams Mode of inheritance for gene: CASR was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Osteogenesis imperfecta v1.36 COL11A2 Eleanor Williams commented on gene: COL11A2: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to keep this gene red as it is associated with Stickler syndrome which is covered by other panels.
Osteogenesis imperfecta v1.36 COL11A1 Eleanor Williams commented on gene: COL11A1: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to keep this gene red as it is associated with Stickler syndrome which is covered by other panels.
Osteogenesis imperfecta v1.36 CASR Eleanor Williams commented on gene: CASR: This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.
Osteogenesis imperfecta v1.36 CASR Eleanor Williams commented on gene: CASR: Associated with Hyperparathyroidism, neonatal, Hypocalcemia, autosomal dominant, Hypocalcemia, autosomal dominant, with Bartter syndrome and Hypocalciuric hypercalcemia, type I in OMIM.

Multiple fractures is listed as one of the clinical phenotypes for Hyperparathyroidism, neonatal in OMIM.

PMID: 22620673 - Tonyushkina et al 2012 - report a case of an unusually severe neonatal Familial Hypocalciuric Hypercalcemia due to a novel CaSR gene mutation that presented with perinatal fractures and moderate hypercalcemia. A heterozygous nucleotide substitution c.1664 T>C in exon 6, resulting in an amino acid change I555T.

PMID: 30376845 - Capozza et al 2018 - report a case of a child with Neonatal severe primary hyperparathyroidism. Phenotype included fracture of the humerus neck and severe osteoporosis. The patient was found to have a homozygous novel mutation of the splicing donor site of the intron 5 ( c.1608 + 1G > A –IVS5 + 1G > A. Both asymptomatic parents were found to be heterozygous.

PMID: 26161261 - Fisher et al 2015 - report two unrelated patients with neonatal severe hyperparathyroidism and de novo R185Q heterozygous inactivating CASR mutations. Patient 2 had multiple rib fractures.

Summary: 3 cases reported of patients with variants in CASR and neonatal severe hyperparathyroidism or severe neonatal Familial Hypocalciuric Hypercalcemia. Patients homo- and hetero-zygous for variants in CASR are reported.
Osteogenesis imperfecta v1.36 B4GALT7 Eleanor Williams commented on gene: B4GALT7: This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.
Osteogenesis imperfecta v1.36 B4GALT7 Eleanor Williams Publications for gene: B4GALT7 were set to 15211654; 26940150
Osteogenesis imperfecta v1.35 B4GALT7 Eleanor Williams commented on gene: B4GALT7: Associated with Ehlers-Danlos syndrome, spondylodysplastic type, 1 (#130070) in OMIM.

PMID: 26940150 - Salter et al 2016 - two unrelated patients with compound heterozygous mutations in B4GALT7. Both showed osteopenia (one with fractures, other patient had mild osteopenia). They review the phenotypes reported in previous cases (Table 1): 1 case with osteopenia reported in Faiyaz‐Ul‐Haque et al. [2004] , 1 case reported in Kresse et al. [1987] (with possible rib fracture).

Summary: 3 cases of patients with homozygous or compound heterozygous variants in B4GALT7 and osteopenia, two with fractures.
Osteogenesis imperfecta v1.35 CREB3L1 Meena Balasubramanian reviewed gene: CREB3L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Osteogenesis imperfecta v1.35 GORAB Eleanor Williams commented on gene: GORAB: PMID: 18997784 - Hennies et al 2008 - Gene is called by previous name of SCYL1BP1
PMID: 28807865 - Takeda et al 2017
Osteogenesis imperfecta v1.35 DSPP Eleanor Williams commented on gene: DSPP: PMID: 29512331 - Taleb et al 2018
PMID: 27973701 - Li et al 2017
Osteogenesis imperfecta v1.35 DSPP Eleanor Williams Publications for gene: DSPP were set to 29512331
Osteogenesis imperfecta v1.34 CREB3L1 Eleanor Williams commented on gene: CREB3L1: 4 cases now reported each in a publication (PMID: 24079343 - whole gene deletion, PMID: 28817112 - 3bp in-frame deletion (c.934_936delAAG [p.Lys312del], PMID: 29936144 - premature stop codon c.1284C>A; p.Tyr428*, PMID: 30657919 - homozygous missense variant (p.(Ala304Val))
Osteogenesis imperfecta v1.34 COL11A2 Eleanor Williams Phenotypes for gene: COL11A2 were changed from Disproportionate Short Stature; Stickler Syndrome, Type III to Disproportionate Short Stature; Stickler Syndrome, Type III; Otospondylomegaepiphyseal dysplasia 184840
Osteogenesis imperfecta v1.33 COL11A1 Eleanor Williams Phenotypes for gene: COL11A1 were changed from Disproportionate Short Stature to Disproportionate Short Stature; ibrochondrogenesis 1228520; Stickler syndrome, type II 604841; Marshall Syndrome 154780
Osteogenesis imperfecta v1.32 COL11A1 Eleanor Williams Publications for gene: COL11A1 were set to
Osteogenesis imperfecta v1.31 GORAB Eleanor Williams Phenotypes for gene: GORAB were changed from Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias to Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias; congenital wrinkly skin; prematurely aged face; extremely short stature; osteoporosis leading to recurrent fractures
Osteogenesis imperfecta v1.30 GORAB Eleanor Williams Publications for gene: GORAB were set to
Osteogenesis imperfecta v1.29 DSPP Eleanor Williams Phenotypes for gene: DSPP were changed from Dentinogenesis imperfecta, Shields type II, 125490; Deafness, autosomal dominant 36, with dentinogenesis, 605594; Dentinogenesis imperfecta, Shields type III, 125500; Dentin dysplasia, type II, 125420 -3 to Dentinogenesis imperfecta, Shields type II, 125490; Deafness, autosomal dominant 36, with dentinogenesis, 605594; Dentinogenesis imperfecta, Shields type III, 125500; Dentin dysplasia, type II, 125420 -3; no fractures
Osteogenesis imperfecta v1.28 DSPP Eleanor Williams Publications for gene: DSPP were set to
Osteogenesis imperfecta v1.27 NBAS Eleanor Williams Phenotypes for gene: NBAS were changed from Short stature, optic nerve atrophy, and Pelger-Huet anomaly, 614800 to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, 614800; bone fragility; immunodeficiency; developmental delay
Osteogenesis imperfecta v1.26 NBAS Eleanor Williams Publications for gene: NBAS were set to
Osteogenesis imperfecta v1.25 CASR Eleanor Williams Phenotypes for gene: CASR were changed from Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias to Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias; neonatal severe hyperparathyroidism 239200; severe hypercalcemia, bone demineralization, multiple fractures; familial hypocalciuric hypercalcemia
Osteogenesis imperfecta v1.24 CASR Eleanor Williams Publications for gene: CASR were set to
Osteogenesis imperfecta v1.23 B4GALT7 Eleanor Williams Publications for gene: B4GALT7 were set to
Osteogenesis imperfecta v1.22 B4GALT7 Eleanor Williams Phenotypes for gene: B4GALT7 were changed from Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias to Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias; Ehlers-Danlos syndrome, spondylodysplastic type, 1 130070
Osteogenesis imperfecta v1.21 CREB3L1 Eleanor Williams Phenotypes for gene: CREB3L1 were changed from osteogenesis imperfecta to Osteogenesis imperfecta, type XVI 616229
Osteogenesis imperfecta v1.20 CREB3L1 Eleanor Williams Publications for gene: CREB3L1 were set to 24079343; 28817112
Osteogenesis imperfecta v1.19 WNT1 Duncan Baker reviewed gene: WNT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 TMEM38B Duncan Baker reviewed gene: TMEM38B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 TAPT1 Duncan Baker reviewed gene: TAPT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 SPARC Duncan Baker reviewed gene: SPARC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 SP7 Duncan Baker reviewed gene: SP7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 SERPINH1 Duncan Baker reviewed gene: SERPINH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 SERPINF1 Duncan Baker reviewed gene: SERPINF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 SEC24D Duncan Baker reviewed gene: SEC24D: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 PPIB Duncan Baker reviewed gene: PPIB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 PLS3 Duncan Baker reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 PLOD2 Duncan Baker reviewed gene: PLOD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 P4HB Duncan Baker reviewed gene: P4HB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 P3H1 Duncan Baker reviewed gene: P3H1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 NOTCH2 Duncan Baker reviewed gene: NOTCH2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 LRP5 Duncan Baker reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 IFITM5 Duncan Baker reviewed gene: IFITM5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 FKBP10 Duncan Baker reviewed gene: FKBP10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 FAM46A Duncan Baker reviewed gene: FAM46A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 CRTAP Duncan Baker reviewed gene: CRTAP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 COL1A2 Duncan Baker reviewed gene: COL1A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 COL1A1 Duncan Baker reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 BMP1 Duncan Baker reviewed gene: BMP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 B3GALT6 Duncan Baker reviewed gene: B3GALT6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 ALPL Duncan Baker reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.19 COL11A2 Duncan Baker edited their review of gene: COL11A2: Added comment: Following discussion with Dr Balasubramanian - rate green; Changed phenotypes: Otospondylomegaepiphyseal dysplasia 184840
Osteogenesis imperfecta v1.19 COL11A1 Duncan Baker edited their review of gene: COL11A1: Added comment: Following discussion with Dr Balasubramanian - rate green; Changed phenotypes: ibrochondrogenesis 1228520, Stickler syndrome, type II 604841; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.19 GORAB Duncan Baker edited their review of gene: GORAB: Added comment: Following discussion with Dr Balasubramanian - rate green; Changed publications: 18997784, 28807865
Osteogenesis imperfecta v1.19 DSPP Duncan Baker edited their review of gene: DSPP: Added comment: Following discussion with Dr Balasubramanian - rate green; Changed publications: 29512331; Changed phenotypes: Dentinogenesis imperfecta 125490, no fractures
Osteogenesis imperfecta v1.19 NBAS Duncan Baker edited their review of gene: NBAS: Added comment: Following discussion with Dr Balasubramanian - rate green. Patient 1: NBAS c.5741G>A p.(Arg1914His); c.3010C>T p.(Arg1004*) in a 10-year old boy with significant short stature, bone fragility requiring treatment with bisphosphonates, developmental delay and immunodeficiency. Patient 2: NBAS c.5741G>A p.(Arg1914His); c.2032C>T p.(Gln678*) in a 5-year old boy with similar presenting features, bone fragility, mild developmental delay, abnormal liver function tests and immunodeficiency. In this study, patient fibroblasts have shown reduced collagen expression, compared to control cells and RNAseq studies, in bone cells show that NBAS is expressed in osteoblasts and osteocytes of rodents and primates. These findings provide proof-of-concept that NBAS mutations have mechanistic effects in bone, and that NBAS variants are a novel cause of bone fragility, which is distinguishable from 'Classical' OI.; Changed publications: 27789416
Osteogenesis imperfecta v1.19 CASR Duncan Baker reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: ; Publications: 22620673; Phenotypes: neonatal severe hyperparathyroidism 239200, severe hypercalcemia, bone demineralization, multiple fractures; Mode of inheritance:
Osteogenesis imperfecta v1.19 B4GALT7 Duncan Baker reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: ; Publications: 26940150; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1 130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.19 CREB3L1 Duncan Baker edited their review of gene: CREB3L1: Added comment: Following discussion with Dr Balasubramanian - rate green. PMID: 29936144 Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta. A homozygous CREB3L1 stop codon mutation in a boy with severe OI, had blue sclera and tooth agenesis. Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%); however, collagen I levels were only reduced in hOBs (5-10%). Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to life-long bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures. PMID: 30657919 A homozygous pathogenic missense variant broadens the phenotypic and mutational spectrum of CREB3L1-related osteogenesis imperfecta. Identified the first homozygous pathogenic missense variant (p.(Ala304Val)) in a patient with lethal OI, which is located within the highly conserved basic leucine zipper domain, four amino acids upstream of the DNA binding domain. In vitro structural modeling and luciferase assays demonstrate that this missense variant affects a critical residue in this functional domain, thereby decreasing the type I collagen transcriptional binding ability. In addition, overexpression of the mutant OASIS protein leads to decreased transcription of the SEC23A and SEC24D genes, which code for components of the coat protein complex type II (COPII), and aberrant OASIS signaling also results in decreased protein levels of SEC24D.; Changed publications: 29936144, 30657919; Changed phenotypes: Osteogenesis imperfecta, type XVI 616229
Osteogenesis imperfecta v1.19 TRPV6 Duncan Baker edited their review of gene: TRPV6: Added comment: Affected infants present at birth with prenatal fractures, shortened ribs, and bowing of long bones, as well as respiratory and feeding difficulties.; Changed phenotypes: hyperparathyroidism and metabolic bone disease 618188
Osteogenesis imperfecta v1.19 NUDT6 Duncan Baker commented on gene: NUDT6: Request from Dr Meena Balasubramian - plausible to cause bone fragility, add to panel if possible
Osteogenesis imperfecta v1.19 COPB2 Duncan Baker edited their review of gene: COPB2: Added comment: Request from Dr Meena Balasubramian - plausible to cause bone fragility, add to panel if possible; Changed phenotypes: Juvenile Osteoporosis
Osteogenesis imperfecta v1.18 WNT1 Eleanor Williams reviewed gene: WNT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 TMEM38B Eleanor Williams reviewed gene: TMEM38B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 TAPT1 Eleanor Williams reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 SPARC Eleanor Williams reviewed gene: SPARC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 SP7 Eleanor Williams reviewed gene: SP7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 SERPINH1 Eleanor Williams reviewed gene: SERPINH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 SERPINF1 Eleanor Williams reviewed gene: SERPINF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 SEC24D Eleanor Williams reviewed gene: SEC24D: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 PPIB Eleanor Williams reviewed gene: PPIB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 PLS3 Eleanor Williams reviewed gene: PLS3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 PLOD2 Eleanor Williams reviewed gene: PLOD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 P4HB Eleanor Williams reviewed gene: P4HB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 P3H1 Eleanor Williams reviewed gene: P3H1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 NOTCH2 Eleanor Williams reviewed gene: NOTCH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 LRP5 Eleanor Williams reviewed gene: LRP5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 IFITM5 Eleanor Williams reviewed gene: IFITM5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 FKBP10 Eleanor Williams reviewed gene: FKBP10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 FAM46A Eleanor Williams reviewed gene: FAM46A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 CRTAP Eleanor Williams reviewed gene: CRTAP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 COL1A2 Eleanor Williams reviewed gene: COL1A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 COL1A1 Eleanor Williams reviewed gene: COL1A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 BMP1 Eleanor Williams reviewed gene: BMP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 B3GALT6 Eleanor Williams reviewed gene: B3GALT6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 ALPL Eleanor Williams reviewed gene: ALPL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 COL11A2 Eleanor Williams reviewed gene: COL11A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 COL11A1 Eleanor Williams reviewed gene: COL11A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 GORAB Eleanor Williams reviewed gene: GORAB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 DSPP Eleanor Williams reviewed gene: DSPP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 NBAS Eleanor Williams reviewed gene: NBAS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 CASR Eleanor Williams reviewed gene: CASR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 B4GALT7 Eleanor Williams reviewed gene: B4GALT7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 CREB3L1 Eleanor Williams reviewed gene: CREB3L1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 TRPV6 Eleanor Williams reviewed gene: TRPV6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Osteogenesis imperfecta v1.18 NUDT6 Eleanor Williams edited their review of gene: NUDT6: Added comment: This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: NUDT6; Suggested initial gene rating: amber; Changed rating: AMBER
Osteogenesis imperfecta v1.18 COPB2 Eleanor Williams edited their review of gene: COPB2: Added comment: This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: COPB2; Suggested initial gene rating: amber; Changed rating: AMBER
Osteogenesis imperfecta v1.17 NUDT6 Eleanor Williams commented on gene: NUDT6: PubMed search did not find any other reports of NUDT6 in association with an Osteogenesis imperfecta phenotype.
Osteogenesis imperfecta v1.17 NUDT6 Eleanor Williams commented on gene: NUDT6
Osteogenesis imperfecta v1.17 COPB2 Eleanor Williams commented on gene: COPB2
Osteogenesis imperfecta v1.17 CREB3L1 Duncan Baker edited their review of gene: CREB3L1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.17 WNT1 Eleanor Williams Source NHS GMS was added to WNT1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 TMEM38B Eleanor Williams Source NHS GMS was added to TMEM38B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 TAPT1 Eleanor Williams Source NHS GMS was added to TAPT1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 SPARC Eleanor Williams Source NHS GMS was added to SPARC.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 SP7 Eleanor Williams Source NHS GMS was added to SP7.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 SERPINH1 Eleanor Williams Source NHS GMS was added to SERPINH1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 SERPINF1 Eleanor Williams Source NHS GMS was added to SERPINF1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 SEC24D Eleanor Williams Source NHS GMS was added to SEC24D.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 PPIB Eleanor Williams Source NHS GMS was added to PPIB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 PLS3 Eleanor Williams Source NHS GMS was added to PLS3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 PLOD2 Eleanor Williams Source NHS GMS was added to PLOD2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 P4HB Eleanor Williams Source NHS GMS was added to P4HB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 P3H1 Eleanor Williams Source NHS GMS was added to P3H1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 NOTCH2 Eleanor Williams Source NHS GMS was added to NOTCH2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 LRP5 Eleanor Williams Source NHS GMS was added to LRP5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 IFITM5 Eleanor Williams Source NHS GMS was added to IFITM5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 FKBP10 Eleanor Williams Source NHS GMS was added to FKBP10.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 FAM46A Eleanor Williams Source NHS GMS was added to FAM46A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 CRTAP Eleanor Williams Source NHS GMS was added to CRTAP.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 COL1A2 Eleanor Williams Source NHS GMS was added to COL1A2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 COL1A1 Eleanor Williams Source NHS GMS was added to COL1A1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 BMP1 Eleanor Williams Source NHS GMS was added to BMP1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 B3GALT6 Eleanor Williams Source NHS GMS was added to B3GALT6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 ALPL Eleanor Williams Source NHS GMS was added to ALPL.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 COL11A2 Eleanor Williams Source NHS GMS was added to COL11A2.
Osteogenesis imperfecta v1.17 COL11A1 Eleanor Williams Source NHS GMS was added to COL11A1.
Osteogenesis imperfecta v1.17 GORAB Eleanor Williams Source NHS GMS was added to GORAB.
Osteogenesis imperfecta v1.17 DSPP Eleanor Williams Source NHS GMS was added to DSPP.
Osteogenesis imperfecta v1.17 NBAS Eleanor Williams Source NHS GMS was added to NBAS.
Osteogenesis imperfecta v1.17 CASR Eleanor Williams Source NHS GMS was added to CASR.
Osteogenesis imperfecta v1.17 B4GALT7 Eleanor Williams Source NHS GMS was added to B4GALT7.
Osteogenesis imperfecta v1.17 CREB3L1 Eleanor Williams Source NHS GMS was added to CREB3L1.
Osteogenesis imperfecta v1.17 TRPV6 Eleanor Williams Source NHS GMS was added to TRPV6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Osteogenesis imperfecta v1.17 NUDT6 Eleanor Williams Source NHS GMS was added to NUDT6.
Rating Changed from No List (delete) to Red List (low evidence)
Osteogenesis imperfecta v1.17 COPB2 Eleanor Williams Source NHS GMS was added to COPB2.
Rating Changed from No List (delete) to Red List (low evidence)
Osteogenesis imperfecta v1.16 COL11A2 Duncan Baker reviewed gene: COL11A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Otospondylomegaepiphyseal dysplasia, Fibrochondrogenesis 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis imperfecta v1.16 COL11A1 Duncan Baker reviewed gene: COL11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fibrochondrogenesis 1, Stickler syndrome, type II; Mode of inheritance: None
Osteogenesis imperfecta v1.16 COPB2 Duncan Baker gene: COPB2 was added
gene: COPB2 was added to Osteogenesis imperfecta. Sources: Expert list
Mode of inheritance for gene: COPB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COPB2 were set to Marom et al 2018 ASBMR: COPB2 Loss of Function Leads to Disrupted Collagen Trafficking and Juvenile Osteoporosis
Phenotypes for gene: COPB2 were set to juvenile osteoporosis
Review for gene: COPB2 was set to AMBER
Added comment: New gene. One report linking to juvenile osteoporosis
Sources: Expert list
Osteogenesis imperfecta v1.16 NUDT6 Duncan Baker gene: NUDT6 was added
gene: NUDT6 was added to Osteogenesis imperfecta. Sources: Expert list
Mode of inheritance for gene: NUDT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT6 were set to Essawi et al A homozygous missense variant in NUDT6 is responsible for an autosomal recessive form of osteogenesis imperfecta.
Phenotypes for gene: NUDT6 were set to recurrent fractures, accompanied with other skeletal manifestations including short-limb dwarfism, mild frontal bossing, bowing of legs and scoliosis.
Review for gene: NUDT6 was set to AMBER
Added comment: New gene, one report linking to OI phenotype.
Sources: Expert list
Osteogenesis imperfecta v1.16 TRPV6 Duncan Baker reviewed gene: TRPV6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29861107; Phenotypes: hyperparathyroidism and metabolic bone disease. Affected infants present at birth with prenatal fractures, shortened ribs, and bowing of long bones, as well as respiratory and feeding difficulties.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.16 GORAB Duncan Baker reviewed gene: GORAB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18997784, PMID: 28807865; Phenotypes: congenital wrinkly skin, prematurely aged face, extremely short stature, osteoporosis leading to recurrent fractures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.16 DSPP Duncan Baker reviewed gene: DSPP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29512331, PMID: 26973538, PMID: 27973701; Phenotypes: Dentinogenesis Imperfecta; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis imperfecta v1.16 NBAS Duncan Baker reviewed gene: NBAS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27789416; Phenotypes: bone fragility, immunodeficiency, developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.16 CREB3L1 Duncan Baker reviewed gene: CREB3L1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29936144, PMID: 30657919; Phenotypes: severe/lethal OI, blue sclera, tooth agenesis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Osteogenesis imperfecta v1.16 TRPV6 Helen Brittain Marked gene: TRPV6 as ready
Osteogenesis imperfecta v1.16 TRPV6 Helen Brittain Added comment: Comment when marking as ready: Sufficient cases. Phenotype (antenatal detection of narrow chest, fractures and bowed femora) is within the spectrum of presentation with OI. Therefore appropriate for inclusion.
Osteogenesis imperfecta v1.16 TRPV6 Helen Brittain Gene: trpv6 has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.16 TRPV6 Helen Brittain Classified gene: TRPV6 as Green List (high evidence)
Osteogenesis imperfecta v1.16 TRPV6 Helen Brittain Added comment: Comment on list classification: Sufficient cases. Presenting with antenatal detection of narrow chest, bowed femora and fractures therefore within the spectrum of OI presentation and could mimic this. Appropriate for inclusion.
Osteogenesis imperfecta v1.16 TRPV6 Helen Brittain Gene: trpv6 has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.15 TRPV6 Helen Brittain gene: TRPV6 was added
gene: TRPV6 was added to Osteogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: TRPV6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPV6 were set to 29861107
Phenotypes for gene: TRPV6 were set to Hyperparathyroidism, transient neonatal, 618188
Review for gene: TRPV6 was set to GREEN
Added comment: 6 unrelated children with skeletal abnormalities detected in the third trimester of pregnancy, who presented at birth with elevated serum PTH and alkaline phosphatase activity, with normal or low ionized calcium. Skeletal anomalies included generalized osteopenia, narrow chest, short ribs with multiple healing fractures, and bowing or fractures of long bones. All affected individuals experienced postnatal respiratory difficulties requiring ventilatory support in the first few weeks to months of life. In addition, most showed poor feeding, with some requiring tube feeding.
Sources: Literature
Osteogenesis imperfecta v1.13 Ellen McDonagh Panel name changed from Osteogenesis Imperfecta to Osteogenesis imperfecta
List of related panels changed from Osteogenesis imperfecta to Osteogenesis Imperfecta
Panel types changed to Rare Disease 100K; GMS Rare Disease
Osteogenesis imperfecta FAM46A Louise Daugherty commented on FAM46A
Osteogenesis imperfecta FAM46A Sarah Leigh reviewed FAM46A
Osteogenesis imperfecta FAM46A Sarah Leigh classified FAM46A as Green List (high evidence)
Osteogenesis imperfecta CREB3L1 BRIDGE consortium reviewed CREB3L1
Osteogenesis imperfecta FAM46A Raymond Dalgleish Added gene to panel
Osteogenesis imperfecta CREB3L1 Sarah Leigh classified CREB3L1 as Amber List (moderate evidence)
Osteogenesis imperfecta TNXB Raymond Dalgleish commented on TNXB
Osteogenesis imperfecta EP300 Louise Daugherty commented on EP300
Osteogenesis imperfecta B3GALT6 Louise Daugherty commented on B3GALT6