线粒体基因组A1555G突变致非综合征性聋患者的临床表型分析  

Analysis of clinical characteristics of patients with non-syndromic hearing impairment induced by mtDNA A1555G mutation

作　　者：丁立才 刘玉和[2] 马楠 钟贞[2] 戚豫[2] 柯肖枚[2] 

机构地区：[1]北京市密云县医院耳鼻咽喉科,北京101500 [2]北京大学第一医院耳鼻咽喉头颈外科,北京100034

出　　处：《中国听力语言康复科学杂志》2008年第3期30-32,共3页Chinese Scientific Journal of Hearing and Speech Rehabilitation

摘　　要：目的评估线粒体基因组(mitochondrial DNA,mtDNA)A1555G突变致非综合征性聋患者的临床表型及听力学特点。方法对经聚合酶链反应-限制性内切酶酶解法证实携带线粒体基因组A1555G突变的96例母系成员,进行病史调查和纯音听阈测试,并对性别、应用氨基糖甙类抗生素史、发病年龄等与耳聋程度的关系进行统计学分析。结果96例研究对象中耳聋患者与正常个体的性别分布均衡,34例有明确的氨基糖甙类抗生素用药史,67例耳聋患者中33例由氨基糖甙类药物耳毒性引起,26例用药后一周内发生耳聋,7例迟发。10个家系的平均耳聋外显率为68.8%。耳聋患者的临床表型多样,耳聋程度与应用氨基糖甙类药物时的年龄以及发病年龄相关,年龄越小,发生耳聋的程度越重;研究对象中年龄大于60岁的9例均为耳聋患者,但耳聋程度相对较轻。结论mtDNA A1555G突变本身不足以引起临床症状,氨基糖甙类药物和核基因在mtDNA A1555G突变的发病机制上起重要作用。携带mtDNA A1555G突变的成员年龄越小,越易出现听力下降,而且耳聋的程度越重。本组资料对耳毒性药物的风险提供了有价值的信息,从而提高氨基糖甙类药物使用的安全性,最终降低耳聋的发生率。Objective To evaluate the clinical characteristics of patients with non-syndromic hearing impairment induced by mtDNA A1555G mutation. Methods The case histories and pure tone audiometry were conducted in 96 matrilineal relatives with mtDNA A1555G mutation which was confirmed by polymerase chain reaction and restriction fragment length polymorphism （PCR-RFLP）. Statistical analysis was done to explore the relationships between the gender, aminoglycoside use, age at onset and hearing impairment in these subjects. Results The gender distribution was balanced between patients with hearing impairment and normal individuals of 96 subjects. The history of aminoglycoside use was confirmed in 34 subjects and 33 of 67 patients were related to aminoglycoside ototoxicity. The hearing impairment in 26 patients was found one week after aminoglycoside administration while the hearing impairment in the other 7 patients was delayed. Ten pedigrees exhibited high percentage of hearing impairment, ranging from 37,5% to 86.9%, with an average of 68,8%. Clinical evaluations revealed the variable phenotype of hearing impairment including audiometric configuration in these patients. The degree of hearing loss in the patients was related to the age of using aminoglycoside and age at onset. The younger the children were, the worse their hearing impairment. Nine patients over 60 years had mild hearing loss, Conclusion MtDNA A1555G mutation itself is not sufficient to produce the clinical phenotypes. Aminoglycosides and nuclear backgrounds appear to be the major modifier factors for the phenotypic manifestation of mtDNA A1555G mutation, The young children carrying mtDNA A1555G mutation are more susceptible to aminoglycosides than the old and their hearing impairment was worse. The data have provided valuable information to predict who may be at risk for ototoxicity and to improve the safe use of aminoglycosides.

关 键 词：非综合征性聋 线粒体基因组A1555G突变 纯音测听 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]