贵州省356例非综合征型聋患者常见致聋基因突变分析

发布时间：2018-05-07 17:35

本文选题：耳聋 + 基因芯片　；参考：《贵州医科大学》2017年硕士论文

【摘要】：目的:分析贵州地区非综合征型聋患者常见耳聋基因突变特点,初步了解该地区耳聋基因热点突变谱系及频率。方法:采集贵州省356例,平均年龄为11.90±12.23岁的非综合征型聋患者外周血3-5ml,予核酸提取试剂盒提取基因组DNA,应用遗传性耳聋基因芯片检测试剂盒对4个常见耳聋基因的的9个突变热点(GJB2 基因 35delG、176del16、235delC、299delAT 突变,SLC26A4基因 IVS7-2AG、2168AG 突变,GJB3 基因 538CT 突变,12SrRNA 基因1555AG和1494CT突变)进行检测。结果:356例非综合征型聋患者,88例(24.72%)检出携带不同基因突变;1例携带GJB2、SLC26A4双基因突变,GJB2基因突变者40例(11.24%)(含前述1例双基因突变者),其中纯合突变19例(5.34%)复合杂合突变5例(1.40%),单杂合突变15例(4.21%);SLC26A4基因突变者29例(8.15%)(含前述1例双基因突变者),其中纯合突变9例(2.53%),单杂合突变19例(5.34%);线粒体DNA12SrRNA基因突变19例(5.34%),其中1555AG均质突变10例(2.81%),1555AG异质突变7例(1.97%),1494CT均质突变2例(0.56%);1例患者携带GJB3基因538CT杂合突变。其中247例民族信息确定的非综合征型聋患者中,汉族耳聋基因突变检出率为35.00%(49/140),少数民族耳聋基因突变检出率为18.69%(20/107),其中汉族突变检出率较少数民族高,差别有统计学意义(χ2=8.012,P=0.005);苗族、布依族、侗族、土家族耳聋基因检出率分别为19.51%(8/41)、11.76%(2/17)、30.00%(6/20)及 12.50%(1/8)(余少数民族因总病例数较少未进行统计学分析),差别无统计学意义(χ2=2.275,P0.05)。结论:贵州地区非综合征型聋患者中以GJB2基因和SLC26A4基因为最主要的致病基因,其中235delC突变为最常见突变位点,其次为IVS7-2AG突变;对贵州省各民族非综合征型聋患者耳聋基因突变热点分析,表明不同民族耳聋患者的耳聋基因突变普和优势突变有一定差异,为该地区开展基因诊断、遗传咨询和预防干预提供有力依据。
[Abstract]:Objective: to analyze the characteristics of common deafness gene mutations in non-syndromic deafness patients in Guizhou and to understand the pedigree and frequency of hot spot mutations of deafness genes in Guizhou. Methods: 356 cases of Guizhou province were collected. Patients with non-syndromic deafness aged 11.90 卤12.23 years old received nucleic acid extraction kit to extract genomic DNA from peripheral blood of 3-5ml. Nine mutations of GJB2 gene in 4 common deafness genes were detected by genetic deafness gene chip assay kit. The mutation of SLC26A4 gene, IVS7-2AG2168AG, 538CT mutation of GJB3 gene, 12s rRNA gene 1555AG and 1494CT mutation, were detected. Results among the 356 cases of non-syndromic deafness, 88 cases (24.72%) were found to be carrying different gene mutations. One case was carrying GJB 2n SLC26A4 double gene mutation. 40 cases had GJB2 gene mutation. (including one case mentioned above, 19 cases were homozygous mutation, 19 cases were 5.34) complex heterozygous process. There were 5 cases with 1.40T, 15 cases with single heterozygous mutation, 29 cases with single mutation of SLC26A4 gene, 29 cases with 8.15A gene mutation (including the one case mentioned above, 9 cases with homozygous mutation, 9 cases with homozygous mutation, 19 cases with single heterozygosity mutation, 19 cases with mitochondrial DNA12SrRNA gene mutation, including 10 cases with 1555AG homogenicity mutation, 10 cases with 2.81A = 1555AG). Heterozygosity 7 cases (1.97%) and 1494 CT homogenous mutation 2 cases (0.56%) carried 538CT heterozygosity of GJB3 gene. Of the 247 non-syndromic deafness patients identified by ethnic information, the mutation rate of deafness gene in Han nationality was 35.00 / 140%, and that in minority nationality was 18.690.20 / 107g. The mutation rate of Han nationality was higher than that of minority nationality (蠂 ~ 2 / 8.012 / P ~ 0.005; Miao nationality). The detectable rate of deafness genes in Buyi, Dong and Tujia were 19.51% and 11.76 / 41 / 11.76 / 2 / 17 / 30.006 / 20, respectively, and 12.50% / 8% of deafness were not statistically analyzed (蠂 22.275%, P 0.05), but the difference was not statistically significant (蠂 22.275%, P 0.05), but the difference was not significant (蠂 22.275%, P 0.05), and the difference was not significant (蠂 22.275%, P 0.05). Conclusion: GJB2 gene and SLC26A4 gene are the main pathogenic genes in non-syndromic deafness patients in Guizhou area. 235delC mutation is the most common mutation site, followed by IVS7-2AG mutation. The hot spot analysis of deafness gene mutation in non-syndromic deafness patients of different nationalities in Guizhou province shows that there are some differences between the common mutation and dominant mutation of deafness gene in different nationalities of deafness patients. Genetic counseling and preventive intervention provide a strong basis.
【学位授予单位】：贵州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R764.43

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