甘肃省375例非综合征型聋患者聋病易感基因突变检测分析

目的 通过对甘肃省部分非综合征型聋患者进行聋病易感基因筛查,从分子水平了解其遗传病因及特点.方法 采集甘肃省375例非综合征型聋患者的外周静脉血5~10 ml,提取基因组DNA,运用SNPscan技术检测GJB2基因2个外显子36个突变位点、SLC26A4基因21个外显子77个突变位点和mtDNA12SrRNA A1555G及C1494T突变.结果 375例非综合征型聋患者中,23例携带mtDNA12SrRNA A1555G均质性突变(6.13%, 23/375),2例携带mtDNA12SrRNA C1494T均质性突变(0.53%, 2/375);检出GJB2基因突变致聋者42例(11.20%, 42/375),其中纯合突变31例(8.27%, 31/375)、复合杂合突变11例(2.93%, 11/375),GJB2基因单杂合突变携带者25例(6.67%,25/375),c.235delC为最常见的突变类型,等位基因频率为8.80%(66/750);检出SLC26A4基因突变致聋者29例(7.73%, 29/375),其中纯合突变17例(4.53%, 17/375)、复合杂合突变12例(3.20%, 12/375),SLC26A4基因单杂合突变携带者14例(3.73%,14/375),c.919-2A>G和c.2168A>G为其最主要的突变类型,等位基因频率分别为5.20%(39/750)和2.0%(15/750).结论 甘肃省部分非综合征型聋患者mt DNA12SrRNA A1555G突变检出率明显高于全国水平(2.83%,57/2016),而GJB2、SLC26A4基因突变检出率与全国水平相近;三个常见聋病易感基因筛查可为25.60%的本组耳聋患者提供明确的分子病因学诊断.

The Detection of Deafness Predisposing Genes Mutation in 375 Nonsyndromic Hearing Loss Patients from Gansu Province

Objective To investigate the molecular genetic causes and their characteristics of deafness from patients with nonsyndromic hearing loss in Gansu province.Methods Peripheral blood samples were obtained from a total of 375 patients with nonsyndromic hearing loss to extract genomic DNA.Three genes of GJB2, mitochondrial DNA 12SrRNA, and SLC26A4 were screened for mutations in our study cohort using SNPscan technology.Results Among 375 patients, 23 patients were found to carry the homoplasmic mtDNA12SrRNA A1555G mutation, and 2 patients were detected to carry the homoplasmic mtDNA12SrRNA C1494T mutation.Forty-two cases(11.2%) were caused by GJB2 mutations, including 31cases(8.3%) of homozygous mutations, 11 patients(2.9%) of compound heterozygous mutations, and 25 cases(6.7%) of single homozygous mutations.c.235delC was the most prevalent GJB2 mutation with the allele frequency of 8.8%.Twenty-nine cases (7.7%) were caused by SLC26A4mutations, including 17cases(4.5%) of homozygous mutations, 12 patients(3.2%) of compound heterozygous mutations, and 16 cases(4.3%) of single homozygous mutations.c.919-2A>G and c.2168A>G were the most common SLC26A4 mutation, the allele frequencies were 5.2% and 2.0%, respectively.Conclusion A high incidence of mtDNA12SrRNAA1555G mutation is found in nonsyndromic hearing loss patients from Gansu province, while the incidence of GJB2 and SLC26A4 mutations is similar to the level of the overall Chinese deaf population.These findings demonstrate that a total of 25.6% of deaf patients have inherited hearing impairment caused by GJB2, SLC26A4, and mitochondrialDNA12SrRNA mutations.As a result 36% patients and family member can acquire effective genetic counseling.