Maternally inherited hearing loss in a large kindred with a novel T7511C mutation in the mitochondrial DNA tRNA(Ser(UCN)) gene

Thirty-six of 43 maternally related members of a large African American fam ily experienced hearing loss. A muscle biopsy specimen from the proband sho wed cytochrome c oxidase (COX)-deficient fibers but no ragged-red fibers; b iochemical analysis showed marked reduction of COX activity. A novel T7511C point mutation in the tRNA(Ser(UCN)) gene was present in almost homoplasmi c levels (>95%) in the blood of 18 of 20 family members, and was also found in lower abundance in the other two. Single-fiber PCR showed that the muta tional load was greater in COX-deficient muscle fibers. The tRNA(Ser(UCN)) gene may be a "hot spot" for mutations associated with maternally transmitt ed hearing loss.