Clinical evaluation and mitochondrial DNA sequence analysis in two Chinese families with aminoglycoside-induced and non-syndromic hearing loss

Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss is associated with the 12S rRNA C1494T mutation in three Han Chinese pedigrees

“…In the previous investigation, we showed the highly variable penetrance and expressivity of hearing loss in 36 Han Chinese families carrying the A1555G mutation (Li et al, 2004b;Young et al, 2005;Zhao et al, 2005b;Dai et al, 2005;Yuan et al, 2005;Tang et al 2007) and three Han Chinese pedigrees carrying the C1494T mutation (Zhao et al 2004;Wang et al, 2005, Han et al 2007). Sequence analysis of complete mitochondrial genomes as well as clinical and genetic valuations in these Chinese pedigrees suggested that five mitochondrial tRNA variants: tRNA Glu A14693G, tRNA Thr T15908C, tRNA Arg T10454C, tRNA Ser(UCN) G7444A and tRNA Cys G5821A, may influence the phenotypic manifestation of the A1555G mutation (Yuan et al, 2005;Young et al, 2006;Zhao et al, 2005b), while the tRNA Ala T5628C variant may have a modifying role in the phenotypic manifestation of the 12S rRNA C1494T mutation in a large Chinese family with hearing loss (Han et al, 2007).…”

“…Of these, the A1555G mutation in the highly conserved A-site of the 12S rRNA has been associated with both aminoglycoside-induced and nonsyndromic hearing loss in many families worldwide (Prezant et al, 1993;Matthijis et al, 1996;Pandya et al, 1997;Usami et al, 1997;Estivill et al, 1998;del Castillo et al, 2003;Li et al 2004a;2004b;;Young et al, 2005;Yuan et al, 2005;Zhao et al, 2005b;Jacobs et al, 2005). However, the homoplasmic C1494T mutation in the highly conserved decoding site of this rRNA has been associated with both aminoglycoside-induced and non-syndromic hearing loss in only three Chinese families and three Spanish pedigrees (Zhao et al, 2004;Wang et al, 2006;Han et al, 2007;Rodriguez-Ballesteros et al, 2006).…”

“…To further investigate the molecular mechanism of maternally transmitted hearing loss, we have initiated a systematic and extended mutational screening of the 12S rRNA gene in several cohorts of hearing-impaired subjects (Li et al, 2004a;Li et al 2005b;Dai et al, 2006;Young et al, 2005;Zhao et al, 2005b;Tang et al, 2007). In the previous investigation, we showed the highly variable penetrance and expressivity of hearing loss in 36 Han Chinese families carrying the A1555G mutation (Li et al, 2004b;Young et al, 2005;Zhao et al, 2005b;Dai et al, 2005;Yuan et al, 2005;Tang et al 2007) and three Han Chinese pedigrees carrying the C1494T mutation (Zhao et al 2004;Wang et al, 2005, Han et al 2007).…”

A novel method of detecting mitochondrial m.1494C>T and m.1555A>G mutations in a single PCR reaction using base-quenched probe

“…It has been reported that several mutations in the mitochondrial DNA (mtDNA), including m.1555A>G [3], m.1494C>T [4], m.1095T>C [5], m.837A>G [6], and m.1291T>C [7] may possibly associate with the sensorineural hearing loss, and mutations of m.1555A>G and m.1494C>T at the highly conserved decoding site of 12S rRNA are well documented being associated to either aminoglycoside antibiotics-induced or non-syndromic hearing loss in families with different ethnic backgrounds [3,4,8,9].…”

“…It has been demonstrated that mutation m.1494C>T might associate with aminoglycoside-induced hearing loss in a large Chinese family [8,10,11]., while the mutation m.1555A>G may contribute to both aminoglycoside-induced and nonsyndromic hearing loss in families worldwide [12,13]. Both m.1555A>G and m.1494C>T mutations locate in a highly conserved region of 12SrRNA that is implicated in aminoglycoside binding in bacteria.…”