杭州萧山地区新生儿听力及耳聋基因筛查结果分析

Analysis of Results of Neonatal Hearing and Deafness Gene Screening in Xiaoshan District of Hangzhou

目的分析杭州市萧山区新生儿常见耳聋基因的突变类型,并对听力及耳聋基因筛查进行评价。方法对2019年7月至2020年4月杭州市萧山区第一人民医院出生的2005例新生儿进行听力筛查,包括瞬态诱发耳声发射(TEOAE)和自动判别听性脑干诱发电位(AABR);同时采用遗传性耳聋相关基因检测试剂盒,对GJB2、SLC26A4、线粒体DNA12S rRNA和GJB3等4个我国常见的耳聋基因的15个突变位点进行检测。结果2005例新生儿中,通过听力初筛1997例(99.6%,1997/2005),复筛未通过者3例(0.15%,3/2005)。2005例新生儿耳聋基因筛查中,检出常见耳聋基因阳性85例,携带率4.24%(85/2005),其中GJB2突变50例(2.49%,50/2005;其中235del C杂合突变占1.9%,38/2005);SLC26A4突变28例(1.40%,28/2005);线粒体DNA12S rRNA突变5例(0.25%,5/2005);GJB3突变1例(0.05%,1/2005);GJB2及SLC26A4双杂合突变1例(0.05%,1/2005)。听力和耳聋基因联合筛查:听力复筛未通过者3例,其中2例GJB2基因235del C位点杂合突变均为左耳重度感音神经性耳聋,1例SLC26A4基因IVS7-2A>G位点杂合突变为右耳极重度感音神经性耳聋;双杂合突变1例,235del C位点及IVS7-2A>G位点突变,但听力筛查通过;2例有家族史,为176-191del 16杂合突变和IVS7-2A>G位点杂合突变,听力筛查均通过。结论GJB2235del C杂合突变是本地区最常见的突变位点。听力筛查和耳聋基因筛查有其互补性。对本地区新生儿进行联合筛查,可早期发现先天性听力障碍患儿,为新生儿耳聋的积极干预和治疗提供指导,为准确估计耳聋相关基因突变频率提供依据。

Objective To analyze the mutation types of common deafness genes in neonates in Xiaoshan district of Hangzhou,and to evaluate the screening results of hearing and deafness genes.Methods A total of 2005 neonates born at Xiaoshan District First People’s Hospital between July 2019 and April 2020 were screened for hearing,included transient evoked otoacoustic emission(TEOAE)and automated auditory brainstem responses(AABR).Furthermore,15 mutation sites of 4 common deafness genes GJB2,SLC26A4,mitochondrial DNA12s rRNA and GJB3 were detected using the genetic deafness-related gene testing kits.Results Among the 2005 newborns,1997(99.6%)passed the primary hearing screening,and 3(0.15%)failed the re-screening.Totally 85 cases(4.24%)were found to be positive for common deafness genes,including 50 cases of GJB2 mutation(2.49%;235del C heterozygous mutation in 38(1.9%),28 cases of SLC26A4 mutation(1.40%),5 cases of mitochondrial DNA12s rRNA mutation(0.25%),1 case of GJB3 mutation(0.05%),and 1 case of double heterozygous mutation of GJB2 and SLC26A4(0.05%).The combined screening for hearing and deafness genes showed that 3 neonates failed the re-screening,including 2 cases of severe left-sided sensorineural deafness with heterozygous GJB2235del C mutation and 1 case of extremely severe right-sided sensorineural deafness with heterozygous SLC26A4 IVS7-2A>G mutation.One neonate with 235del C and IVS7-2A>G mutations and 2 neonate with family history and heterozygous 176-191del 16 mutation and IVS7-2A>G mutation passed the hearing screening.Conclusion Heterozygous 235del C mutation is the most common mutation in Xiaoshan district of Hangzhou.Hearing screening and deafness gene screening are complementary.The combined screening can early detect congenital hearing impairment and provide guidance for active intervention and treatment of deafness in newborns.Our study provides a basis for accurate estimation of deafness-related gene mutation frequency.