Infantile dilated X-linked cardiomyopathy, G4.5 mutations, altered lipids, and ultrastructural malformations of mitochondria in heart, liver, and skeletal muscle

摘要: Mutations in the Xq28 gene G4.5 lead to dilated cardiomyopathy (DCM). Differential splicing of results a family proteins called "tafazzins" with homology acyltransferases. These enzymes assemble fatty acids into membrane lipids. We sequenced two kindreds X-linked DCM and unrelated men, one idiopathic other arrhythmogenic right ventricular dysplasia. examined ultrastructure heart, liver, muscle biopsy specimens these three types; we used gas chromatography compare acid composition autopsy patients kindred 1 that controls. In DCM, had stop codon (E188X), nonsense mutation, an amino substitution (G240R), missense 2. men isolated was not mutated. Ultrastructural mitochondrial malformations were present tissues DCM. Cardiac both exhibited greatly enlarged mitochondria large bundles stacked, compacted, disarrayed cristae differed from those types Autopsy tissue decreased unsaturated increased saturated concentrations. Seven 13 published mutations, including presented here, occur acyltransferase motifs. Impaired function could result saturation would decrease fluidity. Mitochondrial proliferation may be attempt compensate for impaired acyltransferase. separates mutations without mutations. Electron microscopy promptly fixed myocardial has role defining differential diagnosis Mutational analysis also serves this purpose.