遗传性耳聋家系线粒体DNA 961delT/insC(n)突变的致病性分析

目的 探讨线粒体DNA 961delT/insC(n)突变与氨基甙类药物性耳聋的相关性.方法 对一个耳聋家系11个成员采集氨基甙类抗生素用药史、进行听力学检查、表型分析,采集外周静脉血样本,从白细胞中提取DNA,用聚合酶链反应扩增线粒体DNA(mtDNA)全序列,对扩增片段进行DNA测序,对发现的基因突变与耳聋表型进行分离分析.结果 参与研究的所有9例母系成员均检出mtDNA 961delT/insC(n)突变.有明确氨基甙类抗生素用药史的4例中只有2例耳聋患者,其中1例为用药之前出现的先天性聋,另1例为用药后38年出现的轻度耳聋.突变不与耳聋共分离.结论 本研究不支持mtDNA 961de1T/insC(n)突变是该家系耳聋的致病突变,mtDNA 961位点附近可能是一个多变异的区域,mtDNA 961delT/insC(n)可能是一个与氨基甙类药物性耳聋不明确相关的多态.

Pathological analysis of mitochondrial DNA mutation 961delT/insC(n)in a Chinese family with hereditary hearing loss

Objective To evaluate the relationship between mitochondrial DNA(mtDNA) 961delT/insC(n) mutation and the aminoglycoside -induced hearing loss in a Chinese family. Methods After obtaining informed consent from 11 members of a family from Shanxi province, the history of aminoglycoside use were taken, general medcine and otolaryngo-logical examination were performed and the venous blood samples of the individuals was collected to extract DNA. Mutation analysis of the whole sequence of the mitochondrial DNA was performed by direct sequence after PCR amplification with 24 primer pairs. Segregation of hearing loss of the family with the mtDNA961delT/insC (n) mutation was analysed. Results Except for two non -maternal family members, all of the nine maternal family members were found to possess mtDNA961delT/insC(n) mutation. Four of the nine individuals who possessed mtDNA961delT/insC(n) mutation had a history of aminoglycoside use. Only two of the four cases had manifestation of sensorineural hearing loss. However, one of the two patients had congenital sensorineural hearing loss, onset before the use of the aminoglycoside; another patient had the hearing loss 38 years after the use of the aminoglyside. The hearing loss of the family do not segregate with the mtD-NA961delT/insC (n) mutation. Conclusion The mtDNA961delT/insC (n) may not be the causative mutation of the pedigree. Our data suggest that mtDNA961delT/insC(n) change is rather a common non-pathogenic polymorphism than the genetic bases of the aminoglycoside-induced hearing loss.