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| Thoracic aortic aneurysm or dissection (GMS) v3.7 | PMEPA1 | Ivone Leong Phenotypes for gene: PMEPA1 were changed from thoracic aortic aneurysm; tall stature; dolichocephaly; abnormal axial skeletal morphology; pes planus to thoracic aortic aneurysm, MONDO:0005396; tall stature; dolichocephaly; abnormal axial skeletal morphology; pes planus; Loeys-Dietz syndrome, MONDO:0018954 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v3.6 | PMEPA1 |
Ivone Leong Tag Q4_23_promote_green tag was added to gene: PMEPA1. Tag Q4_23_NHS_review tag was added to gene: PMEPA1. |
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| Thoracic aortic aneurysm or dissection (GMS) v3.6 | PMEPA1 | Ivone Leong Classified gene: PMEPA1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v3.6 | PMEPA1 |
Ivone Leong Added comment: Comment on list classification: New gene submitted by Andrew Mumford (University of Bristol). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. PMID: 36928819 describes 8 families with truncating variants affecting the same polycytosine area in this gene. In the 100KGP cohort, three families of European ancestry with FTAAD have the same variant. This same variant was identified independently in 3 families of Japanese ancestry in a separate Japanese patient group. A second variant in the same polycycstine stretch was identified in a different FTAAD case enrolled in the 100KGP pilot programme. A third variant (5 bp deletion in the same stretch which caused a frameshift mutation) was identified in a family in Belgium. "All pedigrees exhibited dominant inheritance of aortic aneurysm disease with incomplete penetrance and skeletal features including pectus deformity, scoliosis and arachnodactyly with complete penetrance". The authors found four HPO terms related to the musculoskeletal system were significantly enriched, which suggested the phenotypic characteristics of the syndromic aortopathy Loeys–Dietz syndrome. Based on the above evidence this gene has been given an Amber gene rating and should be promoted to Green at the next GMS review. |
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| Thoracic aortic aneurysm or dissection (GMS) v3.6 | PMEPA1 | Ivone Leong Gene: pmepa1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v3.5 | PMEPA1 | Ivone Leong Publications for gene: PMEPA1 were set to PMID:36928819 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v3.1 | PMEPA1 |
Andrew Mumford gene: PMEPA1 was added gene: PMEPA1 was added to Thoracic aortic aneurysm or dissection (GMS). Sources: Research Mode of inheritance for gene: PMEPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PMEPA1 were set to PMID:36928819 Phenotypes for gene: PMEPA1 were set to thoracic aortic aneurysm; tall stature; dolichocephaly; abnormal axial skeletal morphology; pes planus Penetrance for gene: PMEPA1 were set to Complete Review for gene: PMEPA1 was set to GREEN Added comment: Association between chain truncation variants in cytoplasmic domain of PMEPA1 and 'Loeys-Dietz' phenotype was established in an association analysis in 100KGP RD main programme, but reproduced in multiple independent pedigrees reported in PMID:36928819. Gene encodes regulator of TGFBeta signalling, a pathway implicated in other familial thoracic aneurysm disorders. Sources: Research |
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