title: Coexistence of mitochondrial 12S rRNA C1494T and CO1/tRNA(Ser(UCN)) G7444A mutations in two Han Chinese pedigrees with aminoglycoside-induced and non-syndromic hearing loss.
abstract: Mutations in mitochondrial DNA are one of the important causes of hearing loss. We report here the clinical, genetic, and molecular characterization of two Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic bilateral hearing loss. Clinical evaluation revealed the wide range of severity, age-at-onset, and audiometric configuration of hearing impairment in matrilineal relatives in these families. The penetrances of hearing loss in these pedigrees were 20% and 18%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss in these seven pedigrees were 10% and 15%. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the presence of the deafness-associated 12S rRNA C1494T and CO1/tRNA(Ser(UCN)) G7444A mutations. Their distinct sets of mtDNA polymorphism belonged to Eastern Asian haplogroup C4a1, while other previously identified six Chinese mitochondrial genomes harboring the C1494T mutation belong to haplogroups D5a2, D, R, and F1, respectively. This suggested that the C1494T or G7444A mutation occurred sporadically and multiplied through evolution of the mitochondrial DNA (mtDNA). The absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in their mtDNA suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the 12S rRNA C1494T and CO1/tRNA(Ser(UCN)) G7444A mutations in those Chinese families. However, aminoglycosides and other nuclear modifier genes play a modifying role in the phenotypic manifestation of the C1494T mutation in these Chinese families.
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors: Huijun
authors: H
authors: Yuan
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors: Jing
authors: J
authors: Chen
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors: Xin
authors: X
authors: Liu
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors: Jing
authors: J
authors: Cheng
authors: Division of Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
authors: Xinjian
authors: X
authors: Wang
authors: Division of Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
authors: Li
authors: L
authors: Yang
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors: Shuzhi
authors: S
authors: Yang
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors: Juyang
authors: J
authors: Cao
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors: Dongyang
authors: D
authors: Kang
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors: Pu
authors: P
authors: Dai
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors: Suoqiang
authors: S
authors: Zhai
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. Electronic address: HDY301@263.com.
authors: Dongyi
authors: D
authors: Han
authors: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. Electronic address: YWY@263.com.
authors: Wie-Yen
authors: WY
authors: Young
authors: Division of Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: min-xin.guan@cchmc.org.
authors: Min-Xin
authors: MX
authors: Guan
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D002681:China; D051545:Cyclooxygenase 1 / Q000235:genetics* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D034381:Hearing Loss / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D012335:RNA, Ribosomal / Q000737:chemistry* / Q000235:genetics*; D012343:RNA, Transfer / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012694:Serine / Q000737:chemistry*
chemical_list: D000617:Aminoglycosides; D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D012694:Serine; D012343:RNA, Transfer; D051545:Cyclooxygenase 1