文献类型：期刊文献

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

作者：Chen J.[1,2];Yang L.[3];Yang A.[2];Zhu Y.[1,2];Zhao J.[2];Sun D.[2];Tao Z.[4];Tang X.[2];Wang J.[2];Wang X.[3];Tsushima A.[3];Lan J.[5];Li W.[2,6];Wu F.[2,7];Yuan Q.[4];Ji J.[2];Feng J.[8];Wu C.[8];Liao Z.[1];Li Z.[1];Greinwald J.H.[9,10];Lu J.[2];Guan M.-X.[2,3,10]

机构：[1]Childrens Hosp, Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA;[2]First Affiliated Hosp, Wenzhou Med Coll, Dept Otolaryngol, Wenzhou, Zhejiang, Peoples R China;[3]Wenzhou Med Coll, Sch Life Sci, Zhejiang Provincial Key Lab Med Genet, Wenzhou, Zhejiang, Peoples R China;[4]Cincinnati Childrens Hosp, Med Ctr, Ctr Hearing & Deafness Res, Cincinnati, OH USA;[5]First Affiliated Hosp, Dept Lab Med, Wenzhou Med Coll, Wenzhou, Zhejiang, Peoples R China;[6]Quzhou Peoples Hosp, Dept Otolaryngol, Quzhou, Zhejiang, Peoples R China;[7]Zhejiang Prov Peoples Hosp, Dept Lab Med, Hangzhou, Zhejiang, Peoples R China;[8]Shaoxing Univ, Coll Med, Dept Lab Med, Affiliated Hosp, Shaoxing, Zhejiang, Peoples R China;[9]Quzhou Special Educ Sch, Quzhou, Zhejiang, Peoples R China;[10]Cincinnati Childrens Hosp, Med Ctr, Div Otolaryngol, Cincinnati, OH USA;[11]Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA

年份：2007

卷号：401

期号：1-2

起止页码：4

外文期刊名：GENE

收录：SCI-EXPANDED(收录号：WOS:000249975600002)、、Scopus(收录号：2-s2.0-34548499092)、WOS

基金：This work was supported by Public Health Service grants RO1DC05230 and RO1DC07696 from the National Institute on Deafness and Other Communication Disorders, and RO1NS44015 from the National Institute of Neurological Disorders and Stroke and grants from National Basic Research Priorities Program of China 2004CCA02200, Ministry of Public Heath of Zhejiang Province 2006A100 and Ministry of Science and Technology of Zhejiang Province 2007G50G2090026 to M.X.G and a grant from Science and Technology bureau of Wenzhou City Y2006A031 Z. L.

语种：英文

外文关键词：hearing loss; 12S rRNA; mitochondrial DNA; penetrance; mutation; Chinese; aminoglycoside ototoxicity

外文摘要：We report here the clinical. genetic and molecular characterization of three 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 28%, 20%, and 15%, with an average of 21%, when arninoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss in these seven pedigrees were 21%, 13% and 8%, with an average of 14%. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the presence of the deafness-associated 12S rRNA C1494T mutation, in addition to distinct sets of mtDNA polymorphism belonging to Eastern Asian haplogroups F1a1, F1a1 and D5a2, respectively. This suggested that the C 1494T mutation occurred sporadically and multiplied through evolution of the mtDNA. The absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in their mtDNA suggests that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the C1494T mutation in those Chinese families. In addition, the lack of significant mutation in the GJB2 gene ruled out the possible involvement of GJB2 in the phenotypic expression of the C1494T mutation in those affected subjects. However, aminoglycosides and other nuclear modifier genes play a modifying role in the phenotypic manifestation of the C1494T mutation in these Chinese families. (c) 2007 Elsevier B.V All rights reserved.