Estivill X, Govea N, Barceló E, Badenas C, Romero E, Moral L, Scozzri R, D'Urbano L, Zeviani M, Torroni A
Medical and Molecular Genetics Center-IRO, Hospital Duran i Reynals, Barcelona, Spain.
Am J Hum Genet. 1998 Jan;62(1):27-35. doi: 10.1086/301676.
Hearing loss involves both genetic and environmental factors. A mutation (A1555G) in the mtDNA has been associated with aminoglycoside-induced and nonsyndromic sensorineural deafness. The pathological significance of this mutation in Caucasoid families has not been established, and its relationship with antibiotic treatment is not well understood. We studied 70 Spanish families with sensorineural deafness (36 congenital and 34 late onset) for the mtDNA A1555G mutation. The A1555G mutation was found in 19 families with maternally transmitted deafness but not in the other 51 families or in 200 control subjects. In 12 families all the patients with the A1555G mutation who received aminoglycosides became deaf, representing 30.3% of the deaf patients in these families. None of the deaf patients from seven other families received aminoglycosides. Overall, only 17.7% of the patients with deafness and the A1555G mutation had been treated with aminoglycosides. The age at onset of deafness was lower (median age 5 years, range 1-52 years) in those treated with aminoglycosides than in those who did not receive antibiotics (median age 20 years, range 1-65 years) (P < .001). The mtDNA of these families belongs to haplotypes common in Europeans. These data indicate that the A1555G mutation accounts for a large proportion of the Spanish families with late-onset sensorineural deafness, that the A1555G mutation has an age-dependent penetrance for deafness (enhanced by treatment with aminoglycosides), and that mtDNA backgrounds probably do not play a major role in disease expression.
听力损失涉及遗传和环境因素。线粒体DNA中的一种突变（A1555G）与氨基糖苷类药物诱发的非综合征性感音神经性耳聋有关。这种突变在白种人家庭中的病理意义尚未明确，其与抗生素治疗的关系也未得到充分理解。我们对70个患有感音神经性耳聋的西班牙家庭（36个先天性耳聋家庭和34个迟发性耳聋家庭）进行了线粒体DNA A1555G突变研究。在19个母系遗传耳聋的家庭中发现了A1555G突变，而在其他51个家庭以及200名对照受试者中未发现该突变。在12个家庭中，所有携带A1555G突变且接受氨基糖苷类药物治疗的患者都出现了耳聋，占这些家庭中耳聋患者的30.3%。其他7个家庭中的耳聋患者均未接受氨基糖苷类药物治疗。总体而言，携带耳聋和A1555G突变的患者中，仅有17.7%接受过氨基糖苷类药物治疗。接受氨基糖苷类药物治疗的患者耳聋发病年龄较低（中位年龄5岁，范围1 - 52岁），低于未接受抗生素治疗的患者（中位年龄20岁，范围1 - 65岁）（P < .001）。这些家庭的线粒体DNA属于欧洲人中常见的单倍型。这些数据表明，A1555G突变在西班牙迟发性感音神经性耳聋家庭中占很大比例，A1555G突变对耳聋具有年龄依赖性的外显率（氨基糖苷类药物治疗会增强这种外显率），并且线粒体DNA背景可能在疾病表现中不起主要作用。
