山东省滨州市特教学校耳聋学生分子病因学分析——GJB2 235delC突变、线粒体DNA 12S rRNA A1555G突变和SLC26A4 ⅣS7-2A>G突变筛查报告

Molecular etiology analysis among students with profound hearing loss in a special education school in Shandong

目的对山东滨州市特教学校学生进行耳聋分子流行病学调查,了解耳聋的常见分子病因。方法对山东省滨州市阳信、无棣、惠民三县特教学校年龄5～19岁的78名重度耳聋学生进行遗传性耳聋问卷调查、全面体格检查、耳鼻咽喉专科检查以及听力学评估(纯音测听和声导抗)等,应用限制性内切酶法分别对GJB2基因235delC突变、线粒体DNA12S rRNA基因A1555G点突变进行分析,应用直接测序法检测SLC26A4基因ⅣS7-2A>G突变。结果非综合征性耳聋74例。其中,10例(13.51%)携带GJB2基因235delC纯合突变,1例(1.35%)携带GJB2基因235delC和299DelAT复合杂合突变,3例(4.05%)携带GJB2基因235delC杂合突变,2例(2.70%)携带GJB2基因299DelAT杂合突变;5例(6.76%)携带线粒体DNA12S rRNA基因A1555G点突变;3例(4.05%)携带SLC26A4基因ⅣS7-2A>G纯合突变,1例(1.35%)携带SLC26A4基因ⅣS7-2A>G杂合突变。18.92%(14/74)的非综合征性耳聋患者携带GJB2基因235delC和SLC26A4基因ⅣS7-2A>G双等位基因突变(纯合突变+复合杂合突变);8.11%(6/74)的非综合征性耳聋患者携带GJB2基因和SLC26A4基因ⅣS7-2A>G单杂合突变。4例综合征性耳聋患者在所检测范围内均未发现突变。结论山东省滨州地区特教学校耳聋患者存在较高的GJB2基因235delC、线粒体DNA12SrRNA基因A1555G和SLC26A4基因ⅣS7-2A>G突变发生率,线粒体DNA12S rRNA基因A1555G突变发生率高于全国平均水平。聋病分子流行病学调查提示山东省滨州地区23.08%的特教学校耳聋患者在分子水平能够明确诊断,另有8.97%的患者有强烈的遗传倾向。准确的耳聋早期诊断、遗传咨询、及时干预和治疗在这一地区的聋哑人群中是非常重要的。

Objective To study molecular epidemiological basis of non-syndromic hearing loss in Binzhou,Shandong province.Methods Seventy eight deaf students were interviewed for medical histories of hearing loss,use of aminoglycosides,and other clinical abnormalities using questionnaires.Audiological and neurological examination included otoscopy,pure-tone audiometry(Madsen 522) and immittance tests(GSI33).GJB2 235delC and mtDNA A1555G mutations were tested by specific restriction enzyme digestion.The hot spot mutation IVS7-2A>G in SLC26A4 was tested by sequencing.Results Seventy four of the 78 participating students were diagnosed with non-syndromic hearing impairment(NSHI),of whom 10(13.51%) showed homozygous GJB2 235delC mutation,1(1.35%) showed compound heterozygous GJB2 235delC mutation and GJB2 299DelAT mutation,3(4.05%) showed heterozygous GJB2 235delC mutation,2(2.70%) showed heterozygous GJB2 299DelAT mutation;5(6.76%) carried mtDNA A1555G mutation;3(4.05%) carried homozygous SLC26A4 IVS7-2A>G mutation,and 1(1.35%) had heterozygous SLC26A4 IVS7-2A>G mutation.Of these 74 students with NSHI,14(18.92%) had diallele mutation of GJB2 235delC and SLC26A4 IVS7-2 A>G(homozygous mutation and compound heterozygous mutation),and 6(8.11%) had single heterozygous mutation of GJB2 or SLC26A4 ⅣS7-2A>G.None of these mutations was detected in the 4 cases with syndrome hearing impairment(SHI).Conclusion Incidence of GJB2 235delC,mtDNA A1555G and SLC26A4 IVS7-2A >G mutations in this deaf population from Binzhou,Shandong province,is high.The incidence of mtDNA A1555G is higher than the average of the overall Chinese deaf population.In Binzhou,23.08% of NSHI can be confirmed by molecular testing and 8.97% have a stong hereditary tendency.