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[YB07-01] Rapidly progressive infantile cardiomyopathy with mitochondrial respiratory chain complex V deficiency due to loss of ATP synthesis
Keywords:mitochondrial cardiomyopathy、Infantile cardiomyopathy、mitochondrial respiratory chain complex V deficiency
[Background] A previous study described four infantile cardiomyopathy patients harboring an m.8528T＞C mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes with poor prognosis. However, the extent to which this mutation is heteroplasmic in heart tissue, or whether synthesis of both ATPase 6 and 8 proteins is impaired, hence causing mitochondrial respiratory chain complex V deficiency in the heart, was not evaluated in the previous study.
[Method] In a Japanese patient with the m.8528T＞C mutation who died within 5.5 months of age from a rapidly progressive cardiomyopathy, we assessed the heteroplasmic status of the mutation in the autopsy heart tissue, ATPase 6 and 8 protein levels by SDS-PAGE/western blotting and the presence of complex V deficiency assessed by BN-PAGE/western blotting.
[Result] The patient showed a high-degree of heteroplasmic m.8528T＞C mutation in the heart muscle (mean 90%). Compared with hearts from control patients, SDS-PAGE/western blotting analysis showed decreased protein levels of both ATPase 6 and 8 in the patient’s heart, and BN-PAGE/western blotting analysis demonstrated a complex V deficiency.
[Conclusion] In a Japanese infantile cardiomyopathy patient with the m.8528T＞C mutation, we demonstrated the mutation is highly heteroplasmic in the patient’s heart and also protein synthesis of ATPase 6, 8 and complex V were impaired in the heart, which causes loss of ATP synthesis. Our findings support the importance of mitochondrial genome sequencing in infantile cardiomyopathy.
[Method] In a Japanese patient with the m.8528T＞C mutation who died within 5.5 months of age from a rapidly progressive cardiomyopathy, we assessed the heteroplasmic status of the mutation in the autopsy heart tissue, ATPase 6 and 8 protein levels by SDS-PAGE/western blotting and the presence of complex V deficiency assessed by BN-PAGE/western blotting.
[Result] The patient showed a high-degree of heteroplasmic m.8528T＞C mutation in the heart muscle (mean 90%). Compared with hearts from control patients, SDS-PAGE/western blotting analysis showed decreased protein levels of both ATPase 6 and 8 in the patient’s heart, and BN-PAGE/western blotting analysis demonstrated a complex V deficiency.
[Conclusion] In a Japanese infantile cardiomyopathy patient with the m.8528T＞C mutation, we demonstrated the mutation is highly heteroplasmic in the patient’s heart and also protein synthesis of ATPase 6, 8 and complex V were impaired in the heart, which causes loss of ATP synthesis. Our findings support the importance of mitochondrial genome sequencing in infantile cardiomyopathy.