A novel mitochondrial 12SrRNA point mutation in parkinsonism, deafness, and neuropathy

The objective of this study was to determine whether a mitochondrial DNA mu tation and defective oxidative phosphorylation are present in a pedigree wi th maternally inherited sensorineural deafness, levodopa-responsive parkins onism, and neuropathy, We sequenced the mitochondrial-encoded ribosomal RNA , cytochrome c oxidase, and transfer RNA genes by cycle sequencing. A polym erase chain reaction-based restriction enzyme assay with mismatched primers was employed to show heteroplasmy of a novel 12SrRNA mutation in the proba nd and to screen control subjects. Spectrophotometric mitochondria respirat ory chain assays were performed in transformed lymphoblasts from the proban d and 12 normal controls. A novel, heteroplasmic, maternally inherited 12Sr RNA point mutation (T1095C) was found in the pedigree, Respiratory chain en zyme analysis in cultured lymphocytes from the proband revealed a significa nt reduction in cytochrome c oxidase activity, Secondary structure predicts that this mutation disrupts a highly conserved loop in the small subunit r ibosomal RNA, which is important in the initiation of mitochondrial protein synthesis, The mutation was not found in 270 controls of diverse ethnic or igins. We conclude that this mutation is pathogenic and causes an oxidative phosphorylation defect by interfering with mitochondrial protein synthesis .