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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 investigate the molecular epidemiology of deafness in Binzhou, Shandong special education schools and to understand the common molecular causes of deafness. Methods A total of 78 severe deafness students aged 5 to 19 years in Yangxin, Wudi and Huimin special schools of Binzhou City of Shandong Province were investigated by questionnaire of hereditary deafness, comprehensive physical examination, special examination of otolaryngology and audiology ( Pure tone audiometry and acoustic guidance). The 235delC mutation of GJB2 gene and the point mutation of A1555G of mitochondrial DNA 12S rRNA gene were analyzed respectively by restriction endonuclease assay. The S726A4 gene ⅣS7-2A> G mutation was detected by direct sequencing. Results 74 cases of non-syndromic deafness. GJB2 gene 235delC homozygous mutation was carried in 10 cases (13.51%), 235delC and 299DelAT mixed mutation in GJB2 gene in 1 case (1.35%), 235delC heterozygous mutation of GJB2 gene in 3 cases (4.05%), 2.70%) carrying 299DelAT heterozygous mutation of GJB2 gene; 5 (6.76%) carrying mitochondrial DNA 12S rRNA gene A1555G point mutation; 3 cases (4.05%) carrying SLC26A4 gene ⅣS7-2A> G homozygous mutation, Carry SLC26A4 gene IVS7-2A> G heterozygous mutation. 18.92% (14/74) patients with non-syndromic deafness carried GJB2 gene 235delC and SLC26A4 gene IVS7-2A> G dual allele mutation (homozygous mutation + compound heterozygous mutation); 8.11% (6/74) Non-syndromic deafness patients carrying GJB2 gene and SLC26A4 gene IVS7-2A> G heterozygous mutation. Four cases of patients with dementia had no mutations in the tested range. Conclusions There is a high incidence of 235delC in GJB2 gene, 12SrRNA gene A1555G and IVS7-2A> G mutation in SLC26A4 gene in the deaf school in Binzhou, Shandong Province. The incidence of mitochondrial DNA 12S rRNA gene A1555G mutation is higher than the national average. Epidemiological survey of deafness disease revealed that 23.08% of special-education deaf patients in Binzhou district of Shandong Province can make a definite diagnosis at molecular level, and another 8.97% of patients have a strong genetic predisposition. Accurate diagnosis of deafness, genetic counseling, timely intervention and treatment of deaf people in this area is very important.