Cosegregation of the G7444A mutation in the mitochondrial COI/tRNA(Ser(UCN)) genes with the 12S rRNA A1555G mutation in a Chinese family with aminoglycoside-induced and nonsyndromic hearing loss.

Abstract

We report here on the characterization of a three-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing impairment. Ten of 17 matrilineal relatives exhibited bilateral and sensorineural hearing impairment. Of these, nine matrilineal relatives, who had a history of exposure to aminoglycosides, exhibited variable severity and audiometric configuration of hearing loss. The dose and age at the time of drug administration seemed to be correlated with the severity of the hearing loss experienced by affected individuals. Sequence analysis of the complete mitochondrial genome in the pedigree showed the presence of homoplasmic A1555G mutation and 37 variants belonging to haplogroup D4a. Of those variants, the G7444A mutation is of special interest as the mutation at this position results in a read-through of the stop condon AGA of the COI message, thereby adding three amino acids (Lys-Gln-Lys) to the C-terminal of the polypeptide. Alternatively, the G7444A 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 G7444A mutation, similar to the deafness-associated A7445G mutation, may lead to a defect in the processing of the L-strand RNA precursor, thus influencing the phenotypic expression of the A1555G mutation. These data also imply that nuclear background plays a role in the aminoglycoside ototoxicity associated with the A1555G mutation in this Chinese pedigree.

• Authors: Huijun Yuan, Yaping Qian, Yanjun Xu, Juyang Cao, Linna Bai, Weidong Shen, Fei Ji, Xin Zhang, Dongyang Kang, Jun Qin Mo, John H Greinwald, Dongyi Han, Suoqiang Zhai, Wie-Yen Young, Min-Xin Guan
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 138A Issue 2 Pg. 133-40 (Oct 01 2005) ISSN: 1552-4825 [Print] United States
• PMID: 16152638 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: (c) 2005 Wiley-Liss, Inc.

Chemical References

• Aminoglycosides
• DNA, Mitochondrial
• RNA, Ribosomal
• RNA, Transfer, Ser
• RNA, ribosomal, 12S
• Electron Transport Complex IV

Topics

• Adolescent
• Adult
• Aged
• Aminoglycosides
• Base Sequence
• Child
• China
• DNA Mutational Analysis
• DNA, Mitochondrial (chemistry, genetics)
• Electron Transport Complex IV (genetics)
• Family Health
• Female
• Hearing Loss (chemically induced, genetics)
• Humans
• Inheritance Patterns
• Male
• Middle Aged
• Molecular Sequence Data
• Pedigree
• Point Mutation (genetics)
• RNA, Ribosomal (genetics)
• RNA, Transfer, Ser (genetics)