Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Skeletal dysplasia v2.223 | ARSK |
Arina Puzriakova gene: ARSK was added gene: ARSK was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARSK were set to 34916232 Phenotypes for gene: ARSK were set to Mucopolysaccharidoses with short stature, coarse facial features and dysostosis multiplex Review for gene: ARSK was set to AMBER Added comment: Verheyen et al. 2022 (PMID: 34916232) reported four affected individuals of two unrelated consanguineous families with homozygous variants c.250C>T, p.(Arg84Cys) and c.560T>A, p.(Leu187Ter) in ARSK, respectively. Patients were affected with skeletal dysplasia, resembling spondyloepiphysial dysplasia. Reverse phenotyping in two individuals from one family revealed additional cardiac and ophthalmological abnormalities. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v2.198 | PRKAR1A | Eleanor Williams Phenotypes for gene: PRKAR1A were changed from Acrodysostosis 1, with or without hormone resistance 101800; Myxoma, intracardiac 255960; Pigmented nodular adrenocortical disease, primary, 1 610489 to Acrodysostosis 1, with or without hormone resistance, OMIM:101800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v2.195 | PRKAR1A |
Eleanor Williams edited their review of gene: PRKAR1A: Added comment: Looking at the mode of inheritance of this gene on the Skeletal dysplasia panel where it is Both mono and bi-allelic. In OMIM and Gene2Phenotype the relevant phenotypes of Acrodysostosis 1, with or without hormone resistance, OMIM:101800 and ACRODYSOSTOSIS respectively are listed with autosomal dominant/monoallelic inheritance. There are several reports of heterozygous variants in PRKAR1A in patients with Acrodysostosis (PMIDs: 21651393, 22464250, 22464252, 28804209, 23425300, 25075981, 26763073). No reports of biallelic variants were found in a search of PubMed. Therefore the recommendation is for the mode of inheritance to be changed to monoallelic only.; Changed mode of pathogenicity: Other; Changed publications to: 21651393, 22464250, 22464252, 28804209, 23425300, 25075981, 26763073; Changed phenotypes to: Acrodysostosis 1, with or without hormone resistance, OMIM:101800; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v2.138 | TMEM251 | Eleanor Williams Phenotypes for gene: TMEM251 were changed from Dysostosis multiplex‐like skeletal dysplasia; severe short stature to Dysostosis multiplex, Ain-Naz type, OMIM:19345; severe short stature | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v2.137 | TMEM251 | Eleanor Williams reviewed gene: TMEM251: Rating: AMBER; Mode of pathogenicity: None; Publications: 33252156; Phenotypes: Dysostosis multiplex, Ain-Naz type, OMIM:19345; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v2.70 | TMEM251 |
Zornitza Stark gene: TMEM251 was added gene: TMEM251 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: TMEM251 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM251 were set to 33252156 Phenotypes for gene: TMEM251 were set to Dysostosis multiplex‐like skeletal dysplasia; severe short stature Review for gene: TMEM251 was set to AMBER Added comment: Two unrelated consanguineous families with homozygous variants (c.133C>T; p.Arg45Trp and c.215dupA; p.Tyr72Ter), with co-segregation data in one family. Preliminary in vitro functional assays conducted - Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.211 | ZSWIM6 |
Eleanor Williams gene: ZSWIM6 was added gene: ZSWIM6 was added to Skeletal dysplasia. Sources: Other Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZSWIM6 were set to 25105228 Phenotypes for gene: ZSWIM6 were set to Acromelic frontonasal dysostosis 603671 Review for gene: ZSWIM6 was set to GREEN Added comment: Associated with Acromelic frontonasal dysostosis #603671 (AD) and Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features #617865 (AD) in OMIM. Acromelic frontonasal dysostosis - OMIM lists the skeletal phenotypes of Patellar hypoplasia or aplasia (in some patients), Tibial hypoplasia, polydactyly of hands and feet, Talipes equinovarus. Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features - OMIM lists the skeletal phenotype of Foot deformities (in some patients) only Sources: Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | RIPPLY2 |
Eleanor Williams Added phenotypes Spondylocostal dysostosis 6 - 616566 for gene: RIPPLY2 Publications for gene RIPPLY2 were changed from to 26238661; 25343988 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | TBX6 | Eleanor Williams Added phenotypes Spondylocostal dysostosis 5 122600 for gene: TBX6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | HES7 | Eleanor Williams Added phenotypes Spondylocostal dysostosis 4, autosomal recessive 613686 for gene: HES7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | LFNG |
Eleanor Williams Added phenotypes Spondylocostal dysostosis 3, autosomal recessive 609813 for gene: LFNG Publications for gene LFNG were changed from to 30196550; 16385447 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | MESP2 |
Eleanor Williams Added phenotypes Spondylocostal dysostosis 2, autosomal recessive 608681 for gene: MESP2 Publications for gene MESP2 were changed from to 15122512; 18485326 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | DLL3 | Eleanor Williams Added phenotypes Spondylocostal dysostosis 1, autosomal recessive 277300 for gene: DLL3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | CTSK | Eleanor Williams Added phenotypes Pycnodysostosis 265800 for gene: CTSK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | DHODH | Eleanor Williams Added phenotypes Miller syndrome (postaxial acrofacial dysostosis) 263750 for gene: DHODH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | EFTUD2 |
Eleanor Williams Added phenotypes Mandibulofacial dysostosis, Guion-Almeida type 610536 for gene: EFTUD2 Publications for gene EFTUD2 were changed from 19334086; 16760738; 22305528 to 16760738; 19334086; 22305528 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | EVC2 | Eleanor Williams Added phenotypes Ellis-van Creveld syndrome 225500; Weyers acrofacial dysostosis 193530 for gene: EVC2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | BMPER | Eleanor Williams Added phenotypes Diaphanospondylodysostosis 608022 for gene: BMPER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | SOST | Eleanor Williams Added phenotypes Craniodiaphyseal dysplasia, autosomal dominant 122860; Van Buchem disease 239100; Sclerosteosis 1 269500 for gene: SOST | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | POLR1A | Eleanor Williams Added phenotypes Acrofacial dysostosis, Cincinnati type 616462 for gene: POLR1A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | SF3B4 | Eleanor Williams Added phenotypes Acrofacial dysostosis 1, Nager type 154400 for gene: SF3B4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | PDE4D | Eleanor Williams Added phenotypes Acrodysostosis 2, with or without hormone resistance 614613 for gene: PDE4D | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.153 | PRKAR1A | Eleanor Williams Added phenotypes Acrodysostosis 1, with or without hormone resistance 101800 for gene: PRKAR1A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | TBX6 | Tracy Lester reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylocostal dysostosis 5 122600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | SOST | Tracy Lester reviewed gene: SOST: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Craniodiaphyseal dysplasia, autosomal dominant 122860, Sclerosteosis 1 269500, Van Buchem disease 239100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | SF3B4 | Tracy Lester reviewed gene: SF3B4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Acrofacial dysostosis 1, Nager type 154400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | RIPPLY2 | Tracy Lester reviewed gene: RIPPLY2: Rating: AMBER; Mode of pathogenicity: ; Publications: 26238661, 25343988; Phenotypes: Spondylocostal dysostosis 6 - 616566; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | PRKAR1A | Tracy Lester reviewed gene: PRKAR1A: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Acrodysostosis 1, with or without hormone resistance 101800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | POLR1A | Tracy Lester reviewed gene: POLR1A: Rating: GREEN; Mode of pathogenicity: ; Publications: 25913037; Phenotypes: Acrofacial dysostosis, Cincinnati type 616462; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | PDE4D | Tracy Lester reviewed gene: PDE4D: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Acrodysostosis 2, with or without hormone resistance 614613; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | MESP2 | Tracy Lester reviewed gene: MESP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 15122512, 18485326; Phenotypes: Spondylocostal dysostosis 2, autosomal recessive 608681; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | LFNG | Tracy Lester reviewed gene: LFNG: Rating: AMBER; Mode of pathogenicity: ; Publications: 16385447, 30196550; Phenotypes: Spondylocostal dysostosis 3, autosomal recessive 609813; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | HES7 | Tracy Lester reviewed gene: HES7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylocostal dysostosis 4, autosomal recessive 613686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | EVC2 | Tracy Lester reviewed gene: EVC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Ellis-van Creveld syndrome 225500, Weyers acrofacial dysostosis 193530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | EFTUD2 | Tracy Lester reviewed gene: EFTUD2: Rating: GREEN; Mode of pathogenicity: ; Publications: 19334086, 16760738, 22305528; Phenotypes: Mandibulofacial dysostosis, Guion-Almeida type 610536; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | DLL3 | Tracy Lester reviewed gene: DLL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylocostal dysostosis 1, autosomal recessive 277300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | DHODH | Tracy Lester reviewed gene: DHODH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Miller syndrome (postaxial acrofacial dysostosis) 263750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | CTSK | Tracy Lester reviewed gene: CTSK: Rating: GREEN; Mode of pathogenicity: ; Publications: 28328823; Phenotypes: Pycnodysostosis 265800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.147 | BMPER | Tracy Lester reviewed gene: BMPER: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Diaphanospondylodysostosis 608022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.146 | SOST | Eleanor Williams reviewed gene: SOST: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v1.145 | SOST |
Eleanor Williams Source NHS GMS was added to SOST. Rating Changed from Green List (high evidence) to Green List (high evidence) |