ONLINE MUTATION REPORT Maternally inherited non-syndromic hearing impairment in a Spanish family with the 7510T>C mutation in the mitochondrial tRNA gene

Inherited hearing impairment is a highly heterogeneous group of disorders. 2 In a majority of cases (about 70%), the hearing loss is non-syndromic, that is, it is not associated with any other clinical feature. It can be transmitted following autosomal (recessive or dominant), X linked, or maternal inheritance patterns. In the nuclear genome, more than 70 loci have been reported to be involved in non-syndromic hearing impairment, and 27 genes have been isolated from their critical intervals. In addition, a number of different mutations in several genes of the mitochondrial genome are responsible for hearing impairment. 4 Some of these mutations result in a variety of additional clinical features in diverse organs. Mitochondrial syndromic hearing loss includes Kearns-Sayre syndrome (MIM 530000), MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MIM 540000), MERRF (myoclonus epilepsy and ragged red fibres; MIM 545000), and MIDD (maternally inherited diabetes mellitus and deafness; MIM 520000). In other cases, intrafamilial and interfamilial phenotypic variation is observed, a mutation causing syndromic or non-syndromic hearing impairment in different patients. This is the case for the 7445A>G mutation, causing hearing loss and palmoplantar keratoderma, and for 7472insC, responsible for hearing loss and neurological disorders (myoclonus epilepsy, ataxia, and cognitive impairment). Finally, other mutations have been associated so far only with hearing loss. These include mutations 7510T>C and 7511T>C in the tRNA gene, and 1095T>C and 1555A>G in the gene for the 12S rRNA. This last mutation is responsible for a dual phenotype, since it also confers increased susceptibility to the ototoxic action of aminoglycoside antibiotics. Most of the mutations causing maternally inherited non-syndromic hearing loss have been described in a small number of families from several countries. The only exception is 1555A>G, which seems to be more frequent than the others, although its real prevalence remains to be determined in most populations. Remarkably, in Spain it may account for about 15-20% of all familial cases of nonsyndromic hearing loss, irrespective of their mode of inheritance and age of onset 24 (unpublished results). The prevalence of other mitochondrial mutations causing hearing loss in the Spanish population is unknown. We investigated the prevalence of the 7510T>C and 1095T>C mutations in the Spanish population, and here we report the genetic and clinical characterisation of a Spanish family with non-syndromic postlingual hearing loss, which includes 26 confirmed carriers of the 7510T>C mutation.