Identification of the gene causing dilated cardiomyopathy with ataxia syndrome (DCMA), a novel Barth syndrome-like condition in the Hutterite population.

摘要

Dilated Cardiomyopathy with Ataxia (DCMA) syndrome is a novel autosomal recessive condition found in the Dariusleut Hutterite population. The clinical features of DCMA include dilated cardiomyopathy, cerebellar ataxia, male genital anomalies and elevated levels of 3-methylglutaconic and 3-methylglutaric acids. DCMA syndrome was mapped to chromosome 3q26.33, and a mutation (IVS3-1G>C), was identified in a previously uncharacterized gene LOC131118. This mutation affects a conserved splice site, resulting in an mRNA splicing defect and a truncated protein lacking the functional domain. The LOC131118 protein contains a conserved DNAJ domain, and is homologous to a group of proteins including the yeast Ylr008cp (Tim14) and Mdj2p proteins. These yeast proteins are known components of the TIM23 protein translocase of the mitochondrial inner membrane suggesting that the phenotype of DCMA syndrome is likely the result of a defect in mitochondrial protein transport. This would be the second human disorder resulting from a defect in this system.