Prevalence and spectrum of XXXX mutations associated with idiopathic dilated cardiomyopathy.

@entity1 @entity3534 @entity70621 @entity712 @entity296 @entity70622 @entity384 @entity74 @entity70620
@entity384 ( @entity384 ) is the most common form of primary @entity296 . It is the most common cause of chronic @entity712 and the most frequent reason for heart transplantation in young adults. There is increasing evidence demonstrating that @entity74 are involved in the pathogenesis of idiopathic @entity384 . Recent studies have shown that genetically defective @entity70620 predisposes animals to @entity384 . However, the association of @entity70620 with @entity384 in @entity1 has not been reported. In the current study, the whole coding region and flanking splice junction sites of the @entity70620 gene were sequenced in 220 unrelated @entity1 with idiopathic @entity384 . The available relatives of the index @entity1 harboring identified mutations and 200 unrelated ethnically matched healthy individuals used as controls were also genotyped for @entity70620 . The functional effect of the @entity70620 mutations was analyzed in silico. As a result, two novel heterozygous @entity70620 mutations, @entity70621 and @entity70622 , were identified in two families with @entity384 , respectively, with a mutational prevalence of ~0.91%. Genetic analyses of the pedigrees showed that in each family, the mutation co-segregated with @entity384 was transmitted as an autosomal dominant trait with complete penetrance. The missense mutations were absent in 400 control chromosomes and the altered @entity3534 were completely conserved evolutionarily across various species. Functional analysis in silico indicated that the @entity70620 mutations were causative. This study firstly reports the association of @entity70620 mutations with enhanced susceptibility to @entity384 in @entity1 , which provides novel insight into the molecular mechanism underpinning @entity384 , and contributes to the development of novel prophylactic and therapeutic strategies for @entity384 .
