Background: Dilated cardiomyopathy (DCM) is characterized by dilatation and contractile dysfunction of the ventricles, particularly the left ventricle. 20-30% of DCM cases are genetically transmitted, with autosomal dominant inheritance being most commonly described. Five loci for autosomal dominant familial DCM have been identified, but none of these genes are known.

Barth syndrome is an X-linked recessive cardioskeletal myopathy. Associated with this disease are neutropenia, abnormal mitochondria (abnormal cristae), growth retardation, and elevated levels of urinary 3-methylglutaconic acid and 2-ethylhydracrylic acid. The gene for Barth syndrome was previously mapped to Xq28, and was recently identified as G4.5, which encodes novel proteins classified as tafazzins. Multiple mutations in G4.5 have already been described for Barth syndrome patients. We describe a G4.5 mutation in one male patient with idiopathic DCM and no other symptoms of Barth syndrome.

Methods: After informed consent was obtained, blood was drawn for cell immortalization and DNA isolation. Single-stranded conformational polymorphism analysis (SSCP) was performed using G4.5 specific primers, and abnormal bands analyzed by DNA sequence analysis.

Results: An abnormal SSCP conformer was identified, and the band was sequenced. A point mutation was identified in the intron 1 splice acceptor consensus sequence (AG to GG) which would theoretically result in the deletion of exon 2. This is currently under investigation. This mutation was previously described by Johnston et al. in a patient with Barth syndrome. The presence of this mutation in a DCM patient without other clinical manifestations associated with Barth syndrome indicates that G4.5 mutations can result in a broad spectrum of phenotypes.

Conclusions: We have identified a G4.5 mutation in one patient with idiopathic DCM, thus indicating that G4.5 mutations are involved not only in Barth syndrome, but may also play a critical role in some cases of DCM.