2725名新生儿耳聋基因热点突变的筛查分析

Analysis of common mutations of deafness-related genes in 2725 newborns

目的 通过调查浙江省绍兴地区2725名新生儿中常见耳聋基因GJB2、GJB3、线粒体12SrRNA和SLC26A4的20个热点突变的携带率、突变类型及其与听力的相关性,为大规模开展聋病基因筛查提供科学依据.方法 应用基质辅助激光解吸电离飞行时间质谱技术（matrix-assisted laser desorptionionization-time of flight-mass spectrometry,MALDI-TOF-MS）进行热点突变检测.结果 2725名新生儿中共检测出突变149例,阳性率5.47％：其中GJB2突变84例,阳性率3.08％;GJB3突变13例,阳性率0.48％;SLC26A4突变49例,阳性率1.80％;线粒体12SrRNA突变3例,阳性率0.11％.检出突变位点共14个,突变频率由高到低依次是GJB2 c.235delC 65例、SLC26A4 IVS7-2A＞G 34例、GJB2c.299-300delAT 13例、GJB3 c.538C＞T 7例、GJB2 c.176_191del16 6例和GJB3 c.547G＞A 6例.结论 常见耳聋基因在绍兴地区新生儿中有较高的阳性率,扩大筛查位点可提高筛查阳性率和突变位点的检出率.除GJB2、线粒体12S rRNA和SLC26A4外,本地区GJB3突变亦有较高的检出率,可能在耳聋发生中起重要作用.

Objective To screen for common mutations of deafness-related genes in order to determine the carrier rate,types of mutation,and their relevance to hearing loss.Methods For 4 deafness-related genes GJB2,GJB3,12S rRNA and SLC26A4,20 common mutations were screened among 2725 newborns from Shaoxing,Zhejiang by matrix-assisted laser desorption ionization-time of flight-mass spectrometry.Results Among the 2725 newborns,149 （5.47%） were diagnosed with mutations,which included 84 （3.08%） with GJB2 mutations,13 （0.48%） with GJB3 mutations,49 （1.80%） with SLC26A4 mutations and 3 （0.11%） with 12S rRNA mutations.Fourteen mutational hotspots were identified.The most common mutations have included GJB2 c.235delC （65 cases）,SLC26A4 IVS7-2A〉G （34 cases）,GJB2 c.299 300delAT （13 cases）,GJB3 c.538C〉T （7 cases）,GJB2 c.176_191del16 （6 cases） and GJB3 c.547G〉A （6 cases）.Conclusion The detecting rate for deafness-related gene mutations has been relatively high.To broaden the screening spectrum may improve such rate.Besides GJB2,12S rRNA,SLC26A4,GJB3 also features a high mutation rate in the region.