Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype.
Orphanet J Rare Dis
; 13(1): 41, 2018 03 15.
Article
em En
| MEDLINE
| ID: mdl-29544503
ABSTRACT
BACKGROUND:
Thoracic and abdominal aortic aneurysms and dissection often develop in hypertensive elderly patients. At higher risk are smokers and those who have a family history of aortic aneurysms. In most affected families, the aortic aneurysms and dissection is inherited in an autosomal dominant manner with decreased penetrance and variable expressivity. Mutations at two chromosomal loci, TAA1 at 11q23 and the TAA2 at 5q13-14, and eight genes, MYLK, MYH11, TGFBR2, TGFBR1, ACTA2, SMAD3, TGFB2, and MAT2A, have been identified as being responsible for the disease in 23% of affected families.RESULTS:
Herein, we inform on the clinical, genetic and pathological characteristics of nine living and deceased members of a large consanguineous Arab family with thoracic aortic aneurysm and dissection who carry a missense mutation c.4471G > T (Ala1491Ser), in exon 27 of MYLK gene. We show a reduced kinase activity of the Ala1491Ser protein compared to wildtype protein. This mutation is expressed as aortic aneurysm and dissection in one of two distinct phenotypes. A severe fatal and early onset symptom in homozygous or mild late onset in heterozygous genotypes.CONCLUSIONS:
We found that MYLK gene Ala1491Ser mutation affect the kinase activity and clinically, it presents with vascular aneurysms and dissection. We describe a distinct genotype phenotype correlation where; heterozygous patients have mild late onset and incomplete penetrance disease compared with the early onset severe and generally fatal outcome in homozygous patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinase de Cadeia Leve de Miosina
/
Proteínas de Ligação ao Cálcio
/
Aneurisma da Aorta Torácica
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Orphanet J Rare Dis
Ano de publicação:
2018
Tipo de documento:
Article