Clinical evaluation and mitochondrial DNA sequence analysis in two Chinese families with aminoglycoside-induced and non-syndromic hearing loss.
We report here the clinical, genetic, and molecular characterization of two Chinese pedigrees with aminoglycoside-induced and non-syndromic hearing impairment. Clinical evaluation revealed the variable phenotype of hearing impairment including audiometric configuration in these subjects. Penetrances of hearing loss in BJ105 and BJ106 pedigrees are 67% and 33%, respectively. In particular, three of 10 affected matrilineal relatives of BJ105 pedigree had aminoglycoside-induced hearing loss, while seven affected matrilineal relatives in BJ105 pedigree and six affected matrilineal relatives in BJ106 pedigree did not have a history of exposure to aminoglycosides. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the identical homoplasmic A1555G mutation and distinct sets of mtDNA variants belonging to haplogroups F3 and M7b. These variants showed no evolutionary conservation, implying that mitochondrial haplotype may not play a significant role in the phenotypic expression of the A1555G mutation in these Chinese pedigrees. However, aminoglycosides and nuclear backgrounds appear to be major modifier factors for the phenotypic manifestation of the A1555G mutation in these Chinese families.
Zhao
Lidong
L
Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
Wang
Qiuju
Q
Qian
Yaping
Y
Li
Ronghua
R
Cao
Juayng
J
Hart
Laura Christine
LC
Zhai
Suoqiang
S
Han
Dongyi
D
Young
Wie-Yen
WY
Guan
Min-Xin
MX
D000617:Aminoglycosides / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002681:China; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D012335:RNA, Ribosomal / Q000235:genetics
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S