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| Mendeliome v1.3032 | ADAMTS6 | Zornitza Stark Marked gene: ADAMTS6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3032 | ADAMTS6 | Zornitza Stark Gene: adamts6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3032 | ADAMTS6 | Zornitza Stark Phenotypes for gene: ADAMTS6 were changed from Aortic aneurysm MONDO:0005160; Connective tissue disorder MONDO:0003900; Congenital heart disease MONDO:0005453 to Connective tissue disorder MONDO:0003900, ADAMTS6-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3013 | ADAMTS6 | Chirag Patel Classified gene: ADAMTS6 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3013 | ADAMTS6 | Chirag Patel Gene: adamts6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3012 | ADAMTS6 |
Chirag Patel gene: ADAMTS6 was added gene: ADAMTS6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADAMTS6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ADAMTS6 were set to PMID: 40657314 Phenotypes for gene: ADAMTS6 were set to Aortic aneurysm MONDO:0005160; Connective tissue disorder MONDO:0003900; Congenital heart disease MONDO:0005453 Review for gene: ADAMTS6 was set to GREEN Added comment: 4 unrelated individuals with thoracic aortic dilatation/aneurysm (3/4), congenital heart defect (3/4), high palate (3/4), hypertelorism (3/4), flat feet (3/4). learning issues/ID (2/4). WES/WGS identified 4 rare predicted deleterious missense variants in ADAMTS6 gene [p.(Leu814Arg), p.(Asp319Asn), p.(Ala147Thr), p.(Ile810Leu)]. 2/4 variants were de novo, 1/4 was inherited (no parental phenotype info), 1/4 unknown status. Note: THSD4 gene, encoding ADAMTSL6, is associated with aortopathy disorder. Functional studies (patient-derived fibroblasts) demonstrated that the variants impair ADAMTS6 secretion or function resulting in increased deposition of FBN1 and FBN2, and therefore extracellular matrix accumulation and microfibril disorganization. One variant, p.(Leu814Arg), further disrupted the Hippo and TGFβ signalling pathways and altered cell adhesion. Adamts6 (S149R/S149R) mice showed ventricular septal defects and accumulation of FBN1 and FBN2 in the outflow tracts. Proposed name of condition: CHAN syndrome (Connective tissue, Heart defect, thoracic Aortic aneurysm, and Neurodevelopmental) syndrome. Sources: Literature |
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