title: Aminoglycoside-induced and non-syndromic hearing loss is associated with the G7444A mutation in the mitochondrial COI/tRNASer(UCN) genes in two Chinese families.
abstract: We report here the clinical, genetic, and molecular characterization of two Chinese families with aminoglycoside induced and non-syndromic hearing impairment. Clinical and genetic evaluations revealed the variable severity and age-of-onset in hearing impairment in these families. Strikingly, there were extremely low penetrances of hearing impairment in these Chinese families. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical G7444A mutation associated with hearing loss. Indeed, the G7444A mutation in the CO1 gene and the precursor of tRNASer(UCN) gene is present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families and 164 Chinese controls. Their mitochondrial genomes belong to the Eastern Asian haplogroups C5a and D4a, respectively. In fact, the occurrence of the G7444A mutation in these several genetically unrelated subjects affected by hearing impairment strongly indicates that this mutation is involved in the pathogenesis of hearing impairment. However, there was the absence of other functionally significant mtDNA mutations in two Chinese pedigrees carrying the G7444A mutation. Therefore, nuclear modifier gene(s) or aminoglycoside(s) may play a role in the phenotypic expression of the deafness-associated G7444A mutation in these Chinese pedigrees.
authors.affiliation: Department of Otolaryngology and Zhejiang Provincial Key Laboratory of Medical Genetics, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yaping
authors.initials: Y
authors.lastname: Qian
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Tang
authors.forename: Jindan
authors.initials: J
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Zhisu
authors.initials: Z
authors.lastname: Liao
authors.forename: Ronghua
authors.initials: R
authors.lastname: Li
authors.forename: Jinzhang
authors.initials: J
authors.lastname: Ji
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.forename: Jianfu
authors.initials: J
authors.lastname: Chen
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Choo
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000293:Adolescent; D000617:Aminoglycosides / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics; D034381:Hearing Loss / Q000139:chemically induced* / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012362:RNA, Transfer, Ser / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D004272:DNA, Mitochondrial; D012362:RNA, Transfer, Ser