title: Very low penetrance of hearing loss in seven Han Chinese pedigrees carrying the deafness-associated 12S rRNA A1555G mutation.
abstract: Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here the clinical, genetic and molecular characterizations of seven Han Chinese pedigrees with aminoglycoside-induced and nonsyndromic bilateral hearing loss. Clinical evaluation revealed the variable phenotype of hearing impairment including severity, age-at-onset and audiometric configuration in these subjects. The penetrance of hearing loss in these pedigrees ranged from 3% to 29%, with an average of 13.6%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss in these seven pedigrees varied from 0% to 17%, with an average of 5.3%. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the presence of the deafness-associated 12S rRNA A1555G mutation, in addition to distinct sets of mtDNA polymorphism belonging to East Asian haplogroups B4, D4, D5 and F1, respectively. This suggested that the A1555G mutation occurred sporadically and multiplied through evolution of the mtDNA in China. Despite the presence of several evolutionary conservative variants in protein-encoding genes, there was the absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in these seven Chinese families. These suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the A1555G mutation in those Chinese families with very low penetrance of hearing loss. However, aminoglycosides appear to be a major modifier factor for the phenotypic manifestation of the A1555G mutation in these Chinese families.
authors.affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zhisu
authors.initials: Z
authors.lastname: Liao
authors.forename: Jindan
authors.initials: J
authors.lastname: Wang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Qian
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Tao
authors.forename: Lenong
authors.initials: L
authors.lastname: Hu
authors.forename: Guomin
authors.initials: G
authors.lastname: Wu
authors.forename: Jinshan
authors.initials: J
authors.lastname: Lan
authors.forename: Xinjian
authors.initials: X
authors.lastname: Wang
authors.forename: Jingzhang
authors.initials: J
authors.lastname: Ji
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Ji
authors.forename: Jinbao
authors.initials: J
authors.lastname: Feng
authors.forename: Jianfu
authors.initials: J
authors.lastname: Chen
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000225:Adenine; D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides; D044466:Asian People / Q000235:genetics*; D002648:Child; D002681:China; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003638:Deafness / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006147:Guanine; D006312:Hearing Loss, Bilateral / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D012335:RNA, Ribosomal / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D017630:Connexins; D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D000072259:Connexin 26; D006147:Guanine; D000225:Adenine