Autosomal and X chromosome structural variants are associated with congenital heart defects in Turner syndrome: The NHLBI GenTAC registry.
Am J Med Genet A
; 170(12): 3157-3164, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27604636
ABSTRACT
Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30-50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein-coding genes (SLC2A3, SLC2A14, and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non-syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. © 2016 Wiley Periodicals, Inc.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Turner
/
Cromossomos Humanos X
/
Variações do Número de Cópias de DNA
/
Cardiopatias Congênitas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article