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| Skeletal dysplasia v4.35 | NEPRO |
Achchuthan Shanmugasundram changed review comment from: PMID:26633546 reported a sister and brother among 31 Saudi Arabian families studied with skeletal dysplasia and homozygous missense variant in NEPRO gene (p.Arg49Cys). PMID:29620724 reported the same homozygous NEPRO variant (p.Arg49Cys) in two brothers of Arab descent with skeletal dysplasia. The disorder is identical to phenotypes reported in PMID:26633546 and haplotype analysis confirmed the founder nature of the variant. PMID:31250547 reported a 13-year-old Indian girl with a different homozygous missense variant (p.Leu145Phe) and with severe short stature and skeletal dysplasia with sparse scalp hair and skin and joint laxity. Her second-cousin parents were heterozygous for the same variant. This gene has been associated with relevant phenotypes in OMIM (MIM #618853), but not in Gene2Phenotype.; to: PMID:26633546 reported a sister and brother among 31 Saudi Arabian families studied with skeletal dysplasia and homozygous missense variant in NEPRO gene (p.Arg49Cys). PMID:29620724 reported the same homozygous NEPRO variant (p.Arg49Cys) in two brothers of Arab descent with skeletal dysplasia. The disorder is identical to phenotypes reported in PMID:26633546 and haplotype analysis confirmed the founder nature of the variant. PMID:31250547 reported a 13-year-old Indian girl with a different homozygous missense variant (p.Leu145Phe) and with severe short stature and skeletal dysplasia with sparse scalp hair and skin and joint laxity. Her second-cousin parents were heterozygous for the same variant. PMID:37294112 reported a 7-year-old girl from an Arabic-speaking community in Eastern Africa with Anauxetic dysplasia 3 and another homozygous NEPRO variant (p.Arg94Cys). She was born to consanguineous parents, who reported that their shared ancestor was of Arab descent. This patient presented with clinically relevant features not previously described in ANXD3: atlantoaxial subluxation, extensive dental anomalies, and a sagittal suture craniosynostosis resulting in scaphocephaly. This gene has been associated with relevant phenotypes in OMIM (MIM #618853), but not in Gene2Phenotype. |
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| 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 |
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| Skeletal dysplasia v2.70 | GZF1 | Eleanor Williams Phenotypes for gene: GZF1 were changed from Larsen syndrome to Larsen syndrome; joint laxity, short stature, and myopia OMIM:617662; joint laxity, short stature, and myopia MONDO:0060556 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.21 | GZF1 | Zornitza Stark reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662, Larsen-like syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.193 | ARSE | Louise Daugherty Tag new-gene-name tag was added to gene: ARSE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.193 | ARSE | Louise Daugherty commented on gene: ARSE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.166 | GZF1 |
Eleanor Williams commented on gene: GZF1: Associated with Joint laxity, short stature, and myopia (#617662) in OMIM and with LARSEN SYNDROME (probable) in Gene2Phenotype. Generalized joint laxity is listed as a phenotype for Larsen syndrome in Gene2Phenotype. PMID: 28475863 - Patel et al 2017 - 2 cases. Family 1 - a multiplex consanguineous Saudi family affected by severe and recurrent large joint dislocation and severe myopia. The index patient also had severe kyphoscoliosis. Both the index patient and her brother had short stature. A homozygous truncating variant in GZF1 was identified (c.865G>T (pGlu289∗). Family 2 - another multiplex consanguineous family affected by severe myopia, retinal detachment, and milder skeletal involvement (generalized joint laxity) A second homozygous truncating GZF1 variant was identified (c.1054dup (p.Thr352Asnfs∗50). Neither variant was present in 2,379 Saudi exomes or the Exome Aggregation Consortium (ExAC) Browser. In functional studies they found using immunofluorescence, strong localization of GZF1 in the developing mouse eye and, to a lesser extent, in the mesenchyme of the developing mouse limb buds. Using 3 patient-derived lymphoblastoid cell lines they found 1,095 genes to be dysregulated in affected individuals. |
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| Skeletal dysplasia v1.153 | CHST3 | Eleanor Williams Added phenotypes Spondyloepiphyseal dysplasia with congenital joint dislocations (recessive Larsen syndrome) 143095 for gene: CHST3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.153 | GZF1 | Eleanor Williams Added phenotypes Larsen syndrome for gene: GZF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.153 | B3GAT3 | Eleanor Williams Added phenotypes Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects, 245600; Larsen alike phenotype (skd incl) for gene: B3GAT3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.153 | ARSE | Eleanor Williams Added phenotypes CDPXL; Chondrodysplasia punctata, X-linked recessive, 302950; CHONDRODYSPLASIA PUNCTATA 1, X-LINKED; X-linked recessive chondrodysplasia punctata for gene: ARSE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.153 | FLNB | Eleanor Williams Added phenotypes Spondylocarpotarsal synostosis syndrome 272460; Atelosteogenesis, type III 108721; Boomerang dysplasia 112310; Atelosteogenesis, type I 108720; Larsen syndrome 150250 for gene: FLNB | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | GZF1 | Tracy Lester reviewed gene: GZF1: Rating: AMBER; Mode of pathogenicity: ; Publications: 28475863; Phenotypes: Larsen syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | FLNB | Tracy Lester reviewed gene: FLNB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Atelosteogenesis, type I 108720, Atelosteogenesis, type III 108721, Boomerang dysplasia 112310, Larsen syndrome 150250, Spondylocarpotarsal synostosis syndrome 272460; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | CHST3 | Tracy Lester reviewed gene: CHST3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondyloepiphyseal dysplasia with congenital joint dislocations (recessive Larsen syndrome) 143095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | B3GAT3 | Tracy Lester reviewed gene: B3GAT3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Larsen alike phenotype (skd incl), Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects, 245600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | ARSE | Tracy Lester reviewed gene: ARSE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: CDPXL, Chondrodysplasia punctata, X-linked recessive, 302950, X-linked recessive chondrodysplasia punctata, CHONDRODYSPLASIA PUNCTATA 1, X-LINKED; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.146 | ARSE | Eleanor Williams reviewed gene: ARSE: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.145 | ARSE |
Eleanor Williams Source NHS GMS was added to ARSE. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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