ClinVar

In a 16-year-old boy with apical hypertrophic cardiomyopathy and neuropathy, Jonckheere et al. (2008) identified a homoplasmic 8529G-A transition in the MTATP8 gene, resulting in a trp55-to-ter (W55X) substitution. The patient was the third child of nonconsanguineous parents, with 2 healthy sibs. Examination at age 16 years revealed dysarthric speech, ataxic gait, positive Trendelenburg sign, reduced tendon reflexes, and bilateral Babinski sign. Cardiac evaluation showed left ventricular hypertrophy concentrated around the apex of the left ventricle. Sensory and motor axonal polyneuropathy was seen on electromyelogram. Reduced complex V activity was measured in the patient's fibroblasts and muscle tissue, and was confirmed in cybrid clones containing patient-derived mitochondrial DNA. Immunoblotting after blue native polyacrylamide gel electrophoresis showed a lack of holocomplex V and increased amounts of mitochondrial ATP synthase subcomplexes. An in-gel activity assay of ATP hydrolysis showed activity of free F(1)-ATPase in the patient's muscle tissue and in the cybrid clones.