| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Skeletal dysplasia v0.288 | BMP5 | Zornitza Stark Phenotypes for gene: BMP5 were changed from Skeletal dysostosis and atrioventricular septal defect to Skeletal dysplasia, MONDO:0018230, BMP5-related; Skeletal dysostosis and atrioventricular septal defect | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.287 | BMP5 |
Chirag Patel changed review comment from: 1 patient with skeletal dysostosis, atrioventricular septal defect, hypermobility, laryngo-tracheo-bronchomalacia and dysmorphic features (malar hypoplasia, short palpebral fissures, short nose, low nasal bridge, anteverted nares, long philtrum, small ears with abnormally folded antihelix). Skeletal survey showed mild thoracolumbar scoliosis, four sacral segments, absent ossification of the inferior pubic rami, and patellar aplasia. Trio WGS identified compound heterozygous loss of function variants in BMP5 (c.88_89del, p.(Gly30Argfs*11) and c.1104+2del, p.(?). Abnormal splicing was proven on the suspected splice variant using maternal fibroblasts. BMP5 expression is confined to specific parts of the skeleton and cartilage in mice and is tightly regulated by different enhancers. Previous studies of chicken embryonic heart development showed BMP5 expression in the endoderm underlying the precardiac mesoderm, the myocardium of the atrioventricular canal and outflow tract regions. Other bone morphogenetic proteins are linked to several genetic skeletal disorders. Sources: Literature; to: 1 patient with skeletal dysostosis, atrioventricular septal defect, hypermobility, laryngo-tracheo-bronchomalacia and dysmorphic features (malar hypoplasia, short palpebral fissures, short nose, low nasal bridge, anteverted nares, long philtrum, small ears with abnormally folded antihelix). Skeletal survey showed mild thoracolumbar scoliosis, four sacral segments, absent ossification of the inferior pubic rami, and patellar aplasia. Trio WGS identified compound heterozygous loss of function variants in BMP5 (c.88_89del, p.(Gly30Argfs*11) and c.1104+2del, p.(?). Abnormal splicing was proven on the suspected splice variant using maternal fibroblasts. BMP5 expression is confined to specific parts of the skeleton and cartilage in mice and is tightly regulated by different enhancers. Previous studies of chicken embryonic heart development showed BMP5 expression in the endoderm underlying the precardiac mesoderm, the myocardium of the atrioventricular canal and outflow tract regions. Other bone morphogenetic proteins are linked to several genetic skeletal disorders. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.287 | BMP5 |
Chirag Patel gene: BMP5 was added gene: BMP5 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: BMP5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BMP5 were set to PMID: 39239663 Phenotypes for gene: BMP5 were set to Skeletal dysostosis and atrioventricular septal defect Review for gene: BMP5 was set to RED Added comment: 1 patient with skeletal dysostosis, atrioventricular septal defect, hypermobility, laryngo-tracheo-bronchomalacia and dysmorphic features (malar hypoplasia, short palpebral fissures, short nose, low nasal bridge, anteverted nares, long philtrum, small ears with abnormally folded antihelix). Skeletal survey showed mild thoracolumbar scoliosis, four sacral segments, absent ossification of the inferior pubic rami, and patellar aplasia. Trio WGS identified compound heterozygous loss of function variants in BMP5 (c.88_89del, p.(Gly30Argfs*11) and c.1104+2del, p.(?). Abnormal splicing was proven on the suspected splice variant using maternal fibroblasts. BMP5 expression is confined to specific parts of the skeleton and cartilage in mice and is tightly regulated by different enhancers. Previous studies of chicken embryonic heart development showed BMP5 expression in the endoderm underlying the precardiac mesoderm, the myocardium of the atrioventricular canal and outflow tract regions. Other bone morphogenetic proteins are linked to several genetic skeletal disorders. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.270 | LFNG | Elena Savva Phenotypes for gene: LFNG were changed from Spondylocostal dysostosis 3, autosomal recessive 609813 to Spondylocostal dysostosis 3, autosomal recessive MIM#609813 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.171 | RIPPLY2 | Zornitza Stark Phenotypes for gene: RIPPLY2 were changed from Spondylocostal dysostosis 6 - 616566 to Spondylocostal dysostosis 6, MIM# 616566 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.167 | RIPPLY2 | Zornitza Stark reviewed gene: RIPPLY2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25343988, 33410135, 32212228, 29761784; Phenotypes: Spondylocostal dysostosis 6, MIM# 616566; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.152 | ARSK |
Paul De Fazio 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; 32856704 Phenotypes for gene: ARSK were set to Mucopolysaccharidosis MONDO:0019249, ARSK-related Review for gene: ARSK was set to GREEN gene: ARSK was marked as current diagnostic Added comment: 4 individuals from 2 unrelated consanguineous families reported with a homozygous missense and an NMD-predicted nonsense variant, who had features of mucopolysaccharidosis such as short stature, coarse facial features and dysostosis multiplex. Urinary GAG excretion was normal by conventional methods, but LC-MS/MS in 2 individuals revealed an increase in specific dermatan sulfate-derived disaccharides. Functional studies showed reduced protein levels and reduced enzyme activity for the nonsense and missense variant respectively. A mouse model also shows a mucopolysaccharidosis phenotype, albeit milder. Rated green (2 families, functional evidence, mouse model). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.103 | TMEM251 | Zornitza Stark Phenotypes for gene: TMEM251 were changed from Dysostosis multiplex‐like skeletal dysplasia; severe short stature to Dysostosis multiplex, Ain-Naz type 619345 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.102 | TMEM251 | Zornitza Stark reviewed gene: TMEM251: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dysostosis multiplex, Ain-Naz type 619345; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.76 | TMEM251 |
Bryony Thompson 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 v0.64 | TBX6 | Zornitza Stark Phenotypes for gene: TBX6 were changed from Spondylocostal dysostosis 5 122600; Spondylocostal dysostosis 5 122600 to Spondylocostal dysostosis 5 122600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.61 | TBX6 | Zornitza Stark reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 33058178, 31015262, 30636772, 28054739, 23335591, 30307510; Phenotypes: Spondylocostal dysostosis 5, 122600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | RIPPLY2 |
Zornitza Stark gene: RIPPLY2 was added gene: RIPPLY2 was added to Skeletal dysplasia. Sources: NHS GMS Mode of inheritance for gene: RIPPLY2 was set to Publications for gene: RIPPLY2 were set to 25343988; 26238661 Phenotypes for gene: RIPPLY2 were set to Spondylocostal dysostosis 6 - 616566 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | LFNG |
Zornitza Stark gene: LFNG was added gene: LFNG was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,Expert list,NHS GMS,Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Red Mode of inheritance for gene: LFNG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LFNG were set to 30196550; 16385447 Phenotypes for gene: LFNG were set to Spondylocostal dysostosis 3, autosomal recessive 609813 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | ZSWIM6 |
Zornitza Stark gene: ZSWIM6 was added gene: ZSWIM6 was added to Skeletal dysplasia. Sources: Other,Expert Review Green 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 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | TBX6 |
Zornitza Stark gene: TBX6 was added gene: TBX6 was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: TBX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: TBX6 were set to Spondylocostal dysostosis 5 122600; Spondylocostal dysostosis 5 122600 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | SOST |
Zornitza Stark gene: SOST was added gene: SOST was added to Skeletal dysplasia. Sources: NHS GMS,Expert,Expert Review Green Mode of inheritance for gene: SOST was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: SOST were set to Craniodiaphyseal dysplasia, autosomal dominant 122860; Van Buchem disease 239100; Sclerosteosis 1 269500 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | SF3B4 |
Zornitza Stark gene: SF3B4 was added gene: SF3B4 was added to Skeletal dysplasia. Sources: Expert list,NHS GMS,Radboud University Medical Center, Nijmegen,Expert Review Green,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: SF3B4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: SF3B4 were set to Acrofacial dysostosis 1, Nager type 154400 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | PRKAR1A |
Zornitza Stark gene: PRKAR1A was added gene: PRKAR1A was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,Expert list,NHS GMS,Expert Review Green,Radboud University Medical Center, Nijmegen,UKGTN,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: PRKAR1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: PRKAR1A were set to Pigmented nodular adrenocortical disease, primary, 1 610489; Acrodysostosis 1, with or without hormone resistance 101800; Myxoma, intracardiac 255960 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | POLR1A |
Zornitza Stark gene: POLR1A was added gene: POLR1A was added to Skeletal dysplasia. Sources: NHS GMS,Expert list,Expert Review Green Mode of inheritance for gene: POLR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR1A were set to 25913037 Phenotypes for gene: POLR1A were set to Acrofacial dysostosis, Cincinnati type 616462 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | PDE4D |
Zornitza Stark gene: PDE4D was added gene: PDE4D was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: PDE4D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: PDE4D were set to Acrodysostosis 2, with or without hormone resistance 614613; Acrodysostosis 2, with or without hormone resistance 614613 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | MESP2 |
Zornitza Stark gene: MESP2 was added gene: MESP2 was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: MESP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MESP2 were set to 15122512; 18485326 Phenotypes for gene: MESP2 were set to Spondylocostal dysostosis 2, autosomal recessive 608681 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | HES7 |
Zornitza Stark gene: HES7 was added gene: HES7 was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: HES7 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HES7 were set to Spondylocostal dysostosis 4, autosomal recessive 613686 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | EVC2 |
Zornitza Stark gene: EVC2 was added gene: EVC2 was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,NHS GMS,Radboud University Medical Center, Nijmegen,UKGTN,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: EVC2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EVC2 were set to Ellis-van Creveld syndrome 225500; Weyers acrofacial dysostosis 193530 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | EVC |
Zornitza Stark gene: EVC was added gene: EVC was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,NHS GMS,Radboud University Medical Center, Nijmegen,UKGTN,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: EVC was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EVC were set to Ellis-van Creveld syndrome, 225500; ECV1; Ellis-van Creveld Syndrome; Ellis-van Creveld syndrome, 225500Weyers acrodental dysostosis, 193530 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | EFTUD2 |
Zornitza Stark gene: EFTUD2 was added gene: EFTUD2 was added to Skeletal dysplasia. Sources: Expert list,NHS GMS,Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Green Mode of inheritance for gene: EFTUD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EFTUD2 were set to 16760738; 22305528; 19334086 Phenotypes for gene: EFTUD2 were set to Mandibulofacial dysostosis, Guion-Almeida type 610536 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | DLL3 |
Zornitza Stark gene: DLL3 was added gene: DLL3 was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: DLL3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DLL3 were set to Spondylocostal dysostosis 1, autosomal recessive 277300 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | DHODH |
Zornitza Stark gene: DHODH was added gene: DHODH was added to Skeletal dysplasia. Sources: Expert list,NHS GMS,Radboud University Medical Center, Nijmegen,Expert Review Green,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: DHODH was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DHODH were set to Miller syndrome (postaxial acrofacial dysostosis) 263750 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | CTSK |
Zornitza Stark gene: CTSK was added gene: CTSK was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,Expert list,NHS GMS,Expert Review Green,Radboud University Medical Center, Nijmegen,UKGTN,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: CTSK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CTSK were set to 28328823 Phenotypes for gene: CTSK were set to Pycnodysostosis 265800 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | BMPER |
Zornitza Stark gene: BMPER was added gene: BMPER was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: BMPER was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BMPER were set to Diaphanospondylodysostosis 608022 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||