Atypical muscle pathology and a survey of cis-mutations in deaf patients harboring a 1555 A-to-G point mutation in the mitochondrial ribosomal RNA gene.

摘要

We investigated three families with maternally inherited deafness associated with a 1555 A-to-G substitution in the 12S ribosomal RNA gene. Probands in these families developed deafness following streptomycin treatment, whereas several family members who did not receive aminoglycoside showed onset of deafness in middle age. One proband had a non-synonymous A14062G mutation in the ND5 gene and the other had a non-synonymous G15221A mutation in the cytochrome b gene and a T1391C mutation in the 12S ribosomal RNA gene, whose importance in disease expression remains to be clarified. Two muscle biopsies from the patients with and without streptomycin treatment, showed similar findings; a moth-eaten appearance with decreased cytochrome c oxidase activity and abnormal mitochondrial morphology. These findings suggest that even without exposure to aminoglycoside the A1555G mutation may impair mitochondrial function and that the mitochondrial abnormalities associated with the A1555G mutation may be expressed in tissues other than those of the auditory system.