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| Ehlers Danlos syndrome with a likely monogenic cause v2.60 | SMAD3 |
Eleanor Williams commented on gene: SMAD3: Note one case with a biallelic variant reported: PMID: 32935439 - Baskin et al 2020 - first report of a LDS patient with biallelic SMAD3 variants (affecting splice site). Proband had classic Loeys-Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected. |
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| Ehlers Danlos syndrome with a likely monogenic cause v2.57 | LTBP1 |
Andžela Lazdāne changed review comment from: Based on the literature homozygous premature truncating LTBP1 variants was reported in eight affected individuals with connective tissue features. In vivo validation with two independent zebrafish lines carrying mutations in LTBP1 induce abnormal collagen fibrillogenesis in skin and intervertebral ligaments and ectopic bone formation on the vertebrae. Sources: Literature; to: Based on the literature homozygous premature truncating LTBP1 variants was reported in eight affected individuals with connective tissue features. In vivo validation with two independent zebrafish lines carrying mutations in LTBP1 induce abnormal collagen fibrillogenesis in skin and intervertebral ligaments and ectopic bone formation on the vertebrae. Sources: Literature |
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| Ehlers Danlos syndrome with a likely monogenic cause v2.57 | LTBP1 |
Andžela Lazdāne gene: LTBP1 was added gene: LTBP1 was added to Ehlers Danlos syndromes. Sources: Literature Mode of inheritance for gene: LTBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LTBP1 were set to PMID: 33991472 Phenotypes for gene: LTBP1 were set to Cutis laxa; craniofacial dysmorphism; altered skeletal development, including short stature; brachydactyly; clinodactyly Penetrance for gene: LTBP1 were set to Complete Review for gene: LTBP1 was set to GREEN Added comment: Based on the literature homozygous premature truncating LTBP1 variants was reported in eight affected individuals with connective tissue features. In vivo validation with two independent zebrafish lines carrying mutations in LTBP1 induce abnormal collagen fibrillogenesis in skin and intervertebral ligaments and ectopic bone formation on the vertebrae. Sources: Literature |
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| Ehlers Danlos syndrome with a likely monogenic cause v2.42 | SKI | Ivone Leong Phenotypes for gene: SKI were changed from Shprintzen-Goldberg syndrome, 182212 to Shprintzen-Goldberg syndrome, OMIM:182212 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ehlers Danlos syndrome with a likely monogenic cause v2.8 | ATP6V0A2 | Ivone Leong Phenotypes for gene: ATP6V0A2 were changed from Cutis laxa, autosomal recessive, type IIA, 219200; Wrinkly skin syndrome, 278250 to Cutis laxa, autosomal recessive, type IIA, OMIM:219200; Wrinkly skin syndrome, OMIM:278250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ehlers Danlos syndrome with a likely monogenic cause v2.4 | EFEMP1 |
Zornitza Stark gene: EFEMP1 was added gene: EFEMP1 was added to Ehlers Danlos syndromes. Sources: Literature Mode of inheritance for gene: EFEMP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EFEMP1 were set to 32006683; 31792352 Phenotypes for gene: EFEMP1 were set to Connective tissue disorder Review for gene: EFEMP1 was set to AMBER Added comment: Monoallelic variants in this gene are associated with a retinal dystrophy. New publications linking bi-allelic variants to a connective tissue disease phenotype: PMID 31792352 reports one individual with a pronounced connective tissue phenotype presenting multiple and recurrent abdominal and thoracic herniae, myopia, hypermobile joints, scoliosis, and thin translucent skin. This individual has no clinical signs of retinal dystrophy. PMID 32006683 reports 2 homozygous siblings (consanguinous) with multiple and recurrent herniae, pelvic and rectal prolapse, huge diverticula, marfanoid habitus, joint laxity, dorsal scoliosis, advanced bone age, pectus excavatum, dysmorphic facial features, and myopia. Both papers mention that studies on EFEMP1−/− mice revealed a phenotypic resemblance. Sources: Literature |
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| Ehlers Danlos syndrome with a likely monogenic cause v1.43 | SKI | Duncan Baker reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ehlers Danlos syndrome with a likely monogenic cause v1.42 | SKI | Eleanor Williams reviewed gene: SKI: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ehlers Danlos syndrome with a likely monogenic cause v1.41 | SKI |
Eleanor Williams Source NHS GMS was added to SKI. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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| Ehlers Danlos syndrome with a likely monogenic cause v1.36 | ABL1 |
Rebecca Foulger gene: ABL1 was added gene: ABL1 was added to Ehlers Danlos syndromes. Sources: Literature missense tags were added to gene: ABL1. Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ABL1 were set to 28288113 Phenotypes for gene: ABL1 were set to Congenital heart defects and skeletal malformations syndrome, 617602 Mode of pathogenicity for gene: ABL1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: ABL1 was set to GREEN Added comment: Added ABL1 to EDS panel as requested by Helen Brittain, clinical fellow. Wang et al, 2017 (PMID:28288113) report ABL1 germline variants cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. 2 variants reported in 4 families, including c.734A>G (p.Tyr245Cys) found to occur in 3 famililes. Included on this EDS panel on advice from Helen Brittain: the kyphosis / scoliosis / velvety skin could overlap with the EDS syndromes panel as a mimic of kyphoscoliotic EDS. Sources: Literature |
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| Ehlers Danlos syndrome with a likely monogenic cause | SKI | Angela Brady reviewed SKI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ehlers Danlos syndrome with a likely monogenic cause | SKI | Neeti Ghali reviewed SKI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ehlers Danlos syndrome with a likely monogenic cause | SKI | Louise Daugherty edited their review of SKI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ehlers Danlos syndrome with a likely monogenic cause | SKI | Louise Daugherty classified SKI as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ehlers Danlos syndrome with a likely monogenic cause | SKI | Louise Daugherty commented on SKI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||