title: Mutations at position 7445 in the precursor of mitochondrial tRNA(Ser(UCN)) gene in three maternal Chinese pedigrees with sensorineural hearing loss.
abstract: We report here the clinical, genetic and molecular characterization of three Chinese pedigrees with nonsyndromic bilateral hearing loss. 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 DNA (mtDNA) showed the known A7445C mutation in two pedigrees and the novel A7445T mutation in another pedigree, in addition to distinct sets of mtDNA polymorphisms belong to Asian haplogroups D4j and F4. Indeed, the A7445C or A7445T mutation in the CO1 and the precursor of tRNA(Ser(UCN)) genes was present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families and 164 Chinese controls. In fact, the A7445C or A7445T mutation results in a read-through of the stop condon AGA of the CO1 message on the H strand of mtDNA, thereby adding three amino acids (Ser-Gln-Lys) to the C-terminal of the polypeptide. However, the mutated polypeptide may retain a partial function. Alternatively, the A7445C or A7445T mutation is adjacent to the site of 3' end endonucleolytic processing of L-strand RNA precursor, spanning tRNA(Ser(UCN)) and ND6 mRNA. Thus, the A7445C or A7445T mutation may also cause a defect in the processing of the L-strand RNA precursor, thus causing mitochondrial dysfunctions. Furthermore, the occurrence of the mutations at position 7445 in these genetically unrelated subjects affected by hearing impairment strongly indicates that mutations at the position 7445 are involved in the pathogenesis of hearing impairment.
authors.affiliation: Department of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Huijun
authors.initials: H
authors.lastname: Yuan
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Guojian
authors.initials: G
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Xinjian
authors.initials: X
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Yang
authors.forename: Aifeng
authors.initials: A
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Dongyang
authors.initials: D
authors.lastname: Kang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
authors.forename: Suoqiang
authors.initials: S
authors.lastname: Zhai
authors.forename: Dongyi
authors.initials: D
authors.lastname: Han
authors.forename: Wie-Yen
authors.initials: WY
authors.lastname: Young
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D010375:Pedigree; D019683:Penetrance; D017354:Point Mutation; D012362:RNA, Transfer, Ser / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D012362:RNA, Transfer, Ser