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

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目的 通过对甘肃省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mt DNA12Sr RNA A1555G及C1494T突变。结果 375例非综合征型聋患者中,23例携带mt DNA12Sr RNA A1555G均质性突变(6.13%,23/375),2例携带m t DNA12Sr RNA 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.235del C为最常见的突变类型,等位基因频率为8.80%(66/750);检出S LC26A4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),S LC26A4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 DNA12Sr RNA A1555G突变检出率明显高于全国水平(2.83%,57/2016),而GJB2、S LC26A4基因突变检出率与全国水平相近;对本组耳聋患者进行三个常见聋病易患基因筛查,可为其中25.60%的患者提供明确的分子病因学诊断。 Objective To investigate genetic susceptibility and characteristics of deafness-susceptible genes in non-syndromic deaf patients in Gansu Province from the molecular level. Methods Peripheral venous blood of 375 patients with nonsyndromic deafness in Gansu province was collected from 5 to 10 ml. Genomic DNA was extracted. 36 mutations of two exons of GJB2 gene, 21 exons of SLC26A4 gene were detected by SNPscan technique Mutated sites and mt DNA12Sr RNA A1555G and C1494T mutations. Results Of 375 patients with nonsyndromic deafness, 23 patients had homozygous mutation of mitochondrial DNA 12Sr RNA A1555G (6.13%, 23/375) and 2 patients with mitochondrial DNA 12Sr RNA C1494T homozygous mutation (0.53%, 2/375) 42 cases (11.20%, 42/375) were detected deafness with GJB2 gene mutation, of which 31 cases were homozygous mutation (8.27%, 31/375), 11 cases (2.93%, 11/375) 25 cases (6.67%, 25/375) were carriers of GJB2 single heterozygous mutation, c.235del C was the most common mutation, and the allele frequency was 8.80% (66/750). The mutation of S LC26A4 gene was detected There were 29 cases with deafness (7.73%, 29/375), including 17 homozygous mutations (4.53%, 17/375), 12 heterozygous mixed mutations (3.20%, 12/375) Among the carriers, 14 (3.73%, 14/375), c.919-2A> G and c.2168A> G were the main types of mutations, with allele frequencies of 5.20% (39/750) and 2.0% (15/750). Conclusion The detection rate of mt DNA12Sr RNA A1555G mutation in some non-syndromic deaf patients in Gansu province was significantly higher than that of national level (2.83%, 57/2016), but the detection rate of GJB2 and S LC26A4 gene mutations was similar to that of national level. Patients with three common deaf disease susceptibility genetic screening, which can provide clear diagnosis of molecular etiology for 25.60% of patients.
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