Maternally inherited cardiomyopathy: clinical and molecular characterization of large kindred harboring the A4300G point mutation in mitochondrial deoxyribonucleic acid

OBJECTIVES The purpose of this study was to describe the clinical and molecular features of large family with maternally inherited cardiomyopathy (MICM). BACKGROUND Recently, several mitochondrial deoxyribonucleic acid (mtDNA) point mutations have been associated with MICM. However, the distinctive clinical and morphologic features of MICM are not fully appreciated. This is partially due to the small size of the reported pedigrees, often lacking detailed clinical and laboratory information. METHODS Clinical and genetic analysis of the family was carried out. RESULTS Echocardiography showed mostly symmetrical hypertrophic cardiomyopathy in 10 family members. The illness had an unfavorable course. Progressive heart failure occurred in three subjects, who eventually died; one individual underwent heart transplantation. Electrocardiographic or echocardiographic signs of cardiac hypertrophy in the absence of significant clinical complaints were observed in five subjects. Neurologic examination was normal. The mutation was detected in blood from all available subjects. Abundance of mutated molecules ranged between 13% and 100% of total mtDN genomes. The severity of the disease could not be foreseen by the proportion of mutation in blood. CONCLUSIONS This report contributes better description of the clinical aspects of MICM and provides important clues to distinguish it from hypertrophic cardiomyopathy. We suggest that mtDN mutations, particularly in the transfer ribonucleic acid for isoleucin, should be systematically searched in patients with MICM. The identification of an underlying maternally inherited mitochondrial DN defect in familial cases of cardiomyopathy may considerably influence the management and genetic counseling of affected patients.