Cilia gene mutations cause atrioventricular septal defects by multiple mechanisms.

ABSTRACT: Atrioventricular septal defects (AVSDs) are a common severe form of congenital heart disease (CHD). In this study we identified deleterious non-synonymous mutations in two cilia genes, Dnah11 and Mks1, in independent N-ethyl-N-nitrosourea-induced mouse mutant lines with heritable recessive AVSDs by whole-exome sequencing. Cilia are required for left/right body axis determination and second heart field (SHF) Hedgehog (Hh) signaling, and we find that cilia mutations affect these requirements differentially. Dnah11^avc4 did not disrupt SHF Hh signaling and caused AVSDs only concurrently with heterotaxy, a left/right axis abnormality. In contrast, Mks1^avc6 disrupted SHF Hh signaling and caused AVSDs without heterotaxy. We performed unbiased whole-geno

SUBMITTER: Burnicka-Turek O 

PROVIDER: S-EPMC5181596 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature