Thoracic aortic aneurysm or dissection

Gene: MFAP5

I don't know

616166 Aortic aneurysm, familial thoracic 9 - syndromic - also pectus and arachnodactyly

Created: 25 Mar 2019, 4:30 p.m.

Barbier et al 2014 Am J Hum Genet 95:736 PMID:25434006 describe one missense variant c.62G>T (p.Trp21Leu) (MAF 0.0036% 10 alleles - quite high) and one nonsense variant (in final exon) c.472C>T (p.Arg158*) (MAF 0.0045% 11 alleles) in patients with syndromic/non-syndromic thoracic aortic aneurysm and dissections and no previous genetic diagnoisis. The nonsense variant segregates in 4 affected family members (also present in one unaffected 83 year-old and two family members with ambiguous phenotypes - incomplete penetrance?) and the missense variant in two affected family members (plus one younger family member with ambigous phenotype). Functional studies on aortic tissue (following surgery) from the missense variant showed disorganisation of the tunica media with loss of smooth muscle cells and showed enhanced TGF-b signaling in patient compared to healthy aorta. Schubert et al 2016 Am J Med Genet A 170A:1288 PMID:26854089 indentified an additional MFAP5 variant in a TAA cohort - patient also as an MYLK variant. Both missense and classified as VUS. MFAP5 variant is c.341G>A p.Arg114Gln (MAF ASJ 0.34% (56 alleles)) and has stronger supporting BI than the MYLK variant.

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.

Created: 20 Feb 2019, 2:17 p.m.

I don't know

PMID: 26854089 carried out exome analysis of 10 patients with thoracic aortic aneurysm. A panel of 23 genes associated with thoracic aortic aneurysm was applied. One proband was found to have rare missense variants in both MFAP5 and MYLK. Five bioinformatics programs predicted the MFAP5 variant to be damaging. It had not been reported previously in ClinVar or HGMD and had a 0.02% MAF in ExAC. No segregation or functional data was provided.

Created: 22 Jan 2019, 12:53 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Thoracic aortic aneurysm

Publications

• PMID: 26854089

PMID:254340062 (2014) report 2 TAAD-affected families with mutations in MFAP5: 1 nonsense p.Arg158* variant, 1 missense Trp21Leu variant). PMID:26854089 (2016) report variants of uncertain significance in MFAP5 (Arg114Gln) and MYLK in a TAA patient.

Created: 29 Jun 2017, 12:12 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Aortic aneurysm, familial thoracic 9, 616166

Publications

• 25434006
• 26854089