Hearing impairment and neurological dysfunction associated with a mutationin the mitochondrial tRNA(Ser(UCN)) gene

We studied a large Dutch family with maternally inherited, progressive, sen sorineural hearing loss in 27 patients. Only in a single family member was the hearing loss accompanied by neurological symptoms including ataxia and dysarthria. DNA analysis of the mitochondrial genome revealed the insertion of a C at nucleotide position 7472 in the tRNA(Ser(UCN)) gene (7472insC mu tation). We determined the percentage of mutant DNA (heteroplasmy) in blood from all family members, and found no correlation between hearing loss and leucocyte heteroplasmy, The 7472insC mutation was previously identified in a smaller family from Sicily with sensorineural hearing loss in 9 family m embers, six of them also presenting neurologically with ataxia and myoclonu s. The presence of the 7472insC mutation in two different pedigrees strongl y supports its pathogenicity. However, the interfamilial difference in pene trance of the neurologic abnormalities is most likely to be strongly influe nced by secondary factors different from the 7472insC mutation, as heteropl asmy or age of the patients were similar in both families. This mutation sh ould therefore be analysed in families with maternally inherited hearing lo ss, irrespective of whether the hearing loss is non-syndromic or accompanie d by neurologic abnormalities.