Document Detail

Mutations at position 7445 in the precursor of mitochondrial tRNA(Ser(UCN)) gene in three maternal Chinese pedigrees with sensorineural hearing loss.
MedLine Citation:
PMID:  18639500     Owner:  NLM     Status:  MEDLINE    
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.
Jing Chen; Huijun Yuan; Jianxin Lu; Xin Liu; Guojian Wang; Yi Zhu; Jing Cheng; Xinjian Wang; Bing Han; Li Yang; Shuzhi Yang; Aifeng Yang; Qing Sun; Dongyang Kang; Xin Zhang; Pu Dai; Suoqiang Zhai; Dongyi Han; Wie-Yen Young; Min-Xin Guan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-23
Journal Detail:
Title:  Mitochondrion     Volume:  8     ISSN:  1567-7249     ISO Abbreviation:  Mitochondrion     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-10-17     Completed Date:  2009-01-05     Revised Date:  2009-02-25    
Medline Journal Info:
Nlm Unique ID:  100968751     Medline TA:  Mitochondrion     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  285-92     Citation Subset:  IM    
Department of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
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MeSH Terms
Asian Continental Ancestry Group / genetics
Base Sequence
DNA Mutational Analysis
DNA, Mitochondrial / genetics*
Hearing Loss, Sensorineural / genetics*
Point Mutation
RNA, Transfer, Ser / genetics*
Grant Support
Reg. No./Substance:
0/DNA, Mitochondrial; 0/RNA, Transfer, Ser

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