非综合征性耳聋儿童GJB2 235delC及线粒体DNA 12S rRNA A1555G突变分析

Screening of GJB2 235delC mutation and mtDNA 12S rRNA A1555G mutation in Chongqing children with non-syndromic hearing impairment

目的对耳聋患儿进行GJB2基因、线粒体DNA A1555G位点突变检测,为遗传性耳聋提供诊断依据。方法对195例耳聋患儿进行遗传性耳聋问卷调查、全面的体格检查、耳鼻咽喉专科检查以及听力学评估(包括纯音测听、脑干诱发电位和耳声发射)。对195例非综合征性感音神经性耳聋患儿及100例健康对照个体分别进行GJB2基因235delC突变、线粒体DNA12S rRNA基因A1555G点突变的限制性内切酶分析。结果195例患儿者中发现GJB2基因235delC纯合突变、235delC与176-191del16复合及235delC与299-300delAT复合突变等共46例耳聋患儿与GJB2基因突变有关,占23.58%。病患组235delC等位基因频率为18.44%,对照组为2.00%(P<0.01)。同时在患儿组还发现了7例线粒体DNA A1555G突变,对照组未发现线粒体DNA A1555G突变。结论重庆市非综合征型耳聋患儿存在较高的GJB2基因235delC和线粒体DNA12S rRNA基因A1555G突变发生率,高于全国平均水平。耳聋基因诊断技术可以应用在地区性耳聋病因调查中有重要的意义。对基因型-表现型相关性的研究对遗传性耳聋的治疗及预期疗效判断、遗传咨询、产前诊断等具有重要意义。

Objective To detect the mutations of GJB2 and mtDNA A1555G in Chongqing children with hereditary hearing loss. Methods Totally 195 deaf children were included to identify their medical history of hearing loss, use of aminoglycosides, and other clinical abnormalities through filling a questionnaire by their parents, with 100 normal children as eontrol. The audiological and neurological examinations of these children were conducted, including otoscopy, pure-tone audiometry, acoustic brainstem evoked response （ABR） and otoaeoustic emission. GJB2 gene 235delc mutation and mtDNA A1555G mutation were detected with specific restriction enzyme digestion. Results Homozygous deletion C at position 233 -235 of GJB2 （235delC） resulted in frameshifl mutation. GJB2 gene mutations were found in 46 patients （23.58%） with hereditary hearing loss. The allelie frequeney of 235delC allele was 18.44% in the hearing loss children and 2.00% in the eontrol ehildren （P 〈 0. 01 ）. Seven hearing loss children were found to carry mtDNAA1555G mutation. Conclusion The ineidence of GJB2 gene and mtDNA A1555G mutations among the deaf-mute ehildren in Chongqing is higher than the average level of overall Chinese deaf population. Molecular genetic sereening for these mutations is effective method to prevent the occurrence of hereditary hearing loss.