Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA mutation in 16 Chinese families: Implication for early detection and prevention of deafness

• Published in: Biochemical and biophysical research communications Vol. 340; no. 1; pp. 194 - 199
• Main Authors: Dai, Pu, Liu, Xin, Han, Dongyi, Qian, Yaping, Huang, Deliang, Yuan, Huijun, Li, Weiming, Yu, Fei, Zhang, Ruining, Lin, Hongyan, He, Yong, Yu, Youjun, Sun, Quanzhu, Qin, Huaiyi, Li, Ronghua, Zhang, Xin, Kang, Dongyang, Cao, Juyang, Young, Wie-Yen, Guan, Min-Xin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.02.2006
• Subjects: 60 APPLIED LIFE SCIENCES; Adolescent; Adult; Aminoglycoside; Child; Child, Preschool; CHILDREN; China - epidemiology; Chinese; Deafness; Deafness - diagnosis; Deafness - epidemiology; Deafness - genetics; Deafness - prevention & control; Detection; DNA; DNA Mutational Analysis; EVALUATION; Family; Female; Genetic Testing - methods; HAZARDS; Humans; Infant; Male; Maternally transmitted; MITOCHONDRIA; Mitochondrial 12S rRNA mutation; Mutation; MUTATIONS; Ototoxicity; Pedigree; Penetrance; PHENOTYPE; Prevalence; Prevention; Prognosis; Risk Assessment - methods; Risk Factors; RNA - genetics; RNA, Ribosomal - genetics; SAFETY; THERAPY; China; Prevention; Deafness; Maternally transmitted; Aminoglycoside; Penetrance; Chinese; Detection; Mitochondrial 12S rRNA mutation; Ototoxicity
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.11.156

Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here the clinical, genetic, and molecular characterization of 16 Chinese pedigrees (a total of 246 matrilineal relatives) with aminoglycoside-induced impairment. Clinical evaluation revealed the variable phenotype of hearing impairment including audiometric configuration in these subjects, although these subjects share some common features: being bilateral and sensorineural hearing impairment. Strikingly, these Chinese pedigrees exhibited extremely low penetrance of hearing loss, ranging from 4% to 18%, with an average of 8%. In particular, nineteen of 246 matrilineal relatives in these pedigrees had aminoglycoside-induced hearing loss. Mutational analysis of the mtDNA in these pedigrees showed the presence of homoplasmic 12S rRNA A1555G mutation, which has been associated with hearing impairment in many families worldwide. The extremely low penetrance of hearing loss in these Chinese families carrying the A1555G mutation strongly supports the notion that the A1555G mutation itself is not sufficient to produce the clinical phenotype. Children carrying the A1555G mutation are susceptible to the exposure of aminoglycosides, thereby inducing or worsening hearing impairment, as in the case of these Chinese families. Using those genetic and molecular approaches, we are able to diagnose whether children carry the ototoxic mtDNA mutation. Therefore, these data have been providing valuable information and technology to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside therapy, and eventually to decrease the incidence of deafness.