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| Aortopathy_Connective Tissue Disorders v1.97 | ADAMTS6 |
Chirag Patel gene: ADAMTS6 was added gene: ADAMTS6 was added to Aortopathy_Connective Tissue Disorders. 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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| Aortopathy_Connective Tissue Disorders v1.67 | THSD4 | Zornitza Stark Marked gene: THSD4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.67 | THSD4 | Zornitza Stark Gene: thsd4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.67 | THSD4 | Zornitza Stark Phenotypes for gene: THSD4 were changed from Thoracic aortic aneurysm and dissection (TAAD) to Aortic aneurysm, familial thoracic 12, MIM# 619825 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.66 | THSD4 | Zornitza Stark reviewed gene: THSD4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aortic aneurysm, familial thoracic 12, MIM# 619825; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.16 | Zornitza Stark removed gene:THSD4-AS1 from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.15 | THSD4 | Chirag Patel Classified gene: THSD4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.15 | THSD4 | Chirag Patel Gene: thsd4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.14 | THSD4 | Chirag Patel Classified gene: THSD4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.14 | THSD4 | Chirag Patel Gene: thsd4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.13 | THSD4 |
Chirag Patel gene: THSD4 was added gene: THSD4 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature Mode of inheritance for gene: THSD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: THSD4 were set to PMID: 32855533 Phenotypes for gene: THSD4 were set to Thoracic aortic aneurysm and dissection (TAAD) Review for gene: THSD4 was set to GREEN gene: THSD4 was marked as current diagnostic Added comment: 5 functional heterozygous variants in THSD4 (two lead to a premature termination codon) found in 5 families with TAAD. Variants segregated with disease in other family members. THSD4 encodes ADAMTSL6, a microfibril-associated protein that promotes fibrillin-1 matrix assembly. The THSD4 variants studied lead to haploinsufficiency or impaired assembly of fibrillin-1 microfibrils. Thsd4+/- mice showed progressive dilation of the thoracic aorta. Histologic examination of aortic samples from a patient carrying a THSD4 variant and from Thsd4+/- mice, revealed typical medial degeneration and diffuse disruption of extracellular matrix. Sources: Literature |
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| Aortopathy_Connective Tissue Disorders v1.12 | THSD4-AS1 | Chirag Patel Classified gene: THSD4-AS1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.12 | THSD4-AS1 | Chirag Patel Gene: thsd4-as1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.11 | THSD4-AS1 | Chirag Patel reviewed gene: THSD4-AS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.11 | THSD4-AS1 | Chirag Patel Classified gene: THSD4-AS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.11 | THSD4-AS1 | Chirag Patel Gene: thsd4-as1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.11 | THSD4-AS1 | Chirag Patel Classified gene: THSD4-AS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.11 | THSD4-AS1 | Chirag Patel Gene: thsd4-as1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aortopathy_Connective Tissue Disorders v1.10 | THSD4-AS1 |
Chirag Patel gene: THSD4-AS1 was added gene: THSD4-AS1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature Mode of inheritance for gene: THSD4-AS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: THSD4-AS1 were set to PMID: 32855533 Phenotypes for gene: THSD4-AS1 were set to Thoracic aortic aneurysm and dissection (TAAD) Review for gene: THSD4-AS1 was set to GREEN gene: THSD4-AS1 was marked as current diagnostic Added comment: 5 functional heterozygous variants in THSD4 (two lead to a premature termination codon) found in 5 families with TAAD. Variants segregated with disease in other family members. THSD4 encodes ADAMTSL6, a microfibril-associated protein that promotes fibrillin-1 matrix assembly. The THSD4 variants studied lead to haploinsufficiency or impaired assembly of fibrillin-1 microfibrils. Thsd4+/- mice showed progressive dilation of the thoracic aorta. Histologic examination of aortic samples from a patient carrying a THSD4 variant and from Thsd4+/- mice, revealed typical medial degeneration and diffuse disruption of extracellular matrix. Sources: Literature |
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