Nonsyndromic Hearing Loss Caused by a Mitochondrial T7511C Mutation

Abstract

Families with maternally transmitted nonsyndromic hearing loss should be investigated for mutations in the tRNA(Ser(UCN)) gene.

Multiple Quantitative Trait Loci Modify Cochlear Hair Cell Degeneration in the Beethoven (Tmc1Bth) Mouse Model of Progressive Hearing Loss DFNA36

“…Mitochondrial mutations have been implicated in some human auditory neuropathy phenotypes (Ishikawa et al 2002;Wang et al 2005) and in modification of age-related hearing loss in mice (Johnson et al 2001). However, we did not observe an effect of gender on the phenotype of F 1 mice or N 2 mice, or an effect of parental gender on N 2 phenotypes (not shown).…”

Mitochondrial rRNA and tRNA and hearing function

“…This mutation often exists in homoplasmy in most matrilineal relatives and in a high level of heteroplasmy in some matrilineal relatives. However, the levels of homoplasmy and heteroplasmy did not correlate with the severity and age of onset of hearing loss [49][50][51][52][53]. Despite sharing some common features, matrilineal relatives of intra-families or inter-families carrying the T7511C mutation exhibited variable severity, age of onset, and progression in hearing loss [49][50][51][52].…”

“…In the mitochondrial tRNA Ser(UCN) gene, five nonsyndromic deafness-associated mutations, A7445G [42][43][44], 7472insC [45][46][47], T7510C [48,84], T7511C [49][50][51][52][53], and G7444A [55][56][57], have been found in families from various ethnic backgrounds. These mutations often occur in homoplasmy or in high levels of heteroplasmy, indicating a high threshold for pathogenicity.…”

“…The T7511C mutation has been identified to be associated with nonsyndromic SNHL in several families from different ethnic groups, including African [49,50], French [52], and Japanese [51]. This mutation often exists in homoplasmy in most matrilineal relatives and in a high level of heteroplasmy in some matrilineal relatives.…”

“…Despite sharing some common features, matrilineal relatives of intra-families or inter-families carrying the T7511C mutation exhibited variable severity, age of onset, and progression in hearing loss [49][50][51][52]. These pedigrees also differ considerably in the penetrance of the T7511C mutation [50][51][52]. The high variability suggests the existence of genetic and/or environmental factors modifying the phenotypic expression of this mutation.…”