The mitochondrial DNA C3303T mutation can cause cardiomyopathy and/or skeletal myopathy

Objective: Several mutations in mitochondrial DNA have been associated with infantile cardiomyopathy, including a C3303T mutation in the mitochondrial transfer RNA(Leu(UUR)) gene. Although this mutation satisfied generally ac cepted criteria for pathogenicity, its causative role remained to be confir med in more families. Our objective was to establish the frequency of the C 3303T mutation and to define its clinical presentation. Study design: Families with cardiomyopathy and maternal inheritance were st udied by polymerase chain reaction/restriction fragment length polymorphism analysis looking for the C3303T mutation. Results: We found the C3303T mutation in 8 patients from 4 unrelated famili es. In one, the clinical presentation was infantile cardiomyopathy; in the second family, proximal limb and neck weakness dominated the clinical pictu re for the first 10 years of life, when cardiac dysfunction became apparent ; in the third family 2 individuals presented with isolated skeletal myopat hy and 2 others with skeletal myopathy and cardiomyopathy; in the fourth fa mily, one patient had fatal infantile cardiomyopathy and the other had a co mbination of skeletal myopathy and cardiomyopathy. Conclusions: Our findings confirm the pathogenicity of the C3303T mutation and suggest that this mutation may not be rare. The C3303T mutation should be considered in the differential diagnosis of skeletal myopathies and card iomyopathy, especially when onset is in infancy.