Exome Sequencing Identifies Candidate Genetic Modifiers of Syndromic and Familial Thoracic Aortic Aneurysm Severity.
J Cardiovasc Transl Res
; 10(4): 423-432, 2017 Aug.
Article
en En
| MEDLINE
| ID: mdl-28550590
ABSTRACT
Thoracic aortic aneurysm (TAA) is a genetic disease predisposing to aortic dissection. It is important to identify the genetic modifiers controlling penetrance and expressivity to improve clinical prognostication. Exome sequencing was performed in 27 subjects with syndromic or familial TAA presenting with extreme phenotypes (15 with severe TAA; 12 with mild or absent TAA). Family-based analysis of a subset of the cohort identified variants, genes, and pathways segregating with TAA severity among three families. A rare missense variant in ADCK4 (p.Arg63Trp) segregated with mild TAA in each family. Genes and pathways identified in families were further investigated in the entire cohort using the optimal unified sequence kernel association test, finding significance for the gene COL15A1 (p = 0.025) and the retina homeostasis pathway (p = 0.035). Thus, we identified candidate genetic modifiers of TAA severity by exome-based study of extreme phenotypes, which may lead to improved risk stratification and development of new medical therapies.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Aneurisma de la Aorta Torácica
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Genes Modificadores
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Secuenciación del Exoma
Tipo de estudio:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
J Cardiovasc Transl Res
Asunto de la revista:
ANGIOLOGIA
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CARDIOLOGIA
Año:
2017
Tipo del documento:
Article