广西地区感音神经性聋人群致病基因SLC26A4的突变研究

发布时间：2018-05-17 16:29

本文选题：广西地区 + 耳聋基因　；参考：《广西中医药大学》2017年硕士论文

【摘要】：目的:通过对广西地区感因神经性聋人群致病基因SLC26A4常见突变位点进行检测,初步分析广西地区耳聋人群中SLC26A4常见耳聋基因突变特点,为临床防聋及治聋提供参考。方法:研究对象为广西都安县、扶绥县及武鸣县3所特殊教育学校的耳聋患者90例、在我院住院接受人工耳蜗植入术的患者43例、来自我院门诊听力筛查未通过的患者40例、突发性耳聋患者137例,共计310例耳聋患者。其中,男194例,女116例;壮族167例,汉127例,瑶族12例,苗族2例,侗族1例,仫佬族1例;语前聋170例,语后聋140例;感音神经性中度聋31例,重度聋24例,极重度聋255例;有耳聋家族史者44例;43例患者接受单侧人工耳蜗植入术,1例接受双侧。所有受检者均采集外周血并提取基因组DNA,进行PCR扩增,应用博奥生物有限公司提供的晶芯?十五项遗传性耳聋基因检测试剂盒(微阵列芯片法)对样本基因组DNA的SLC26A4的8个突变位点进行检测,并对未确诊的阳性结果进行基因全序列分析。结果:1.310例中,9例存在耳聋基因突变,阳性率为2.90%(9/310),其中,IVS7-2AG杂合突变4例(1.29%,4/310),1229CT纯合突变1例(0.32%,1/310),1229CT杂合突变1例(0.32%,1/310),SLC26A4 1226GA复合杂合突变1例(0.32%,1/310),IVS7-2AG/IVS11+47T㧐C/1548insC复合杂合突变2例(0.65%,2/310)。2.汉族突变4例,阳性率为3.15%(4/127),其中,1229CT杂合突变1例(0.79%,1/127),1229CT纯合突变1例(0.79%,1/127);IVS7-2AG杂合突变2例(1.57%,2/127)。壮族突变5例,阳性率为2.99%(5/167),其中IVS7-2AG杂合突变2例(1.20%,2/167),IVS7-2AG/IVS11+47T㧐C/1548insC复合杂合突变2例(1.20%,2/167),SLC26A4 1226GA复合杂合突变1例(0.60%,1/167)。壮族与汉族之间的差异无统计学意义。3.耳聋家族史患者44例中,3例患者出现SLC26A4基因突变阳性(6.82%,3/44)。4.SLC26A4在聋校患者90例中突变3例(3.33%,3/90)、人工耳蜗43例突变2例(4.65%,2/43)、听力筛查未通过患者突变2例(5%,2/40)、突发性耳聋患者中尚未发现相关基因突变。结论:1.广西地区感音神经性聋患者SLC26A4的8个常见致聋位点突变检出率较全国平均水平偏低,主要以IVS7-2AG突变位点为主。2.广西地区壮族与汉族感音神经性聋患者之间常见致聋基因突变率的比较无明显差异;3.IVS11+47TC位点和1548insC位点为新发现的2个突变位点,广西地区可能存在罕见的致聋基因突变位点。
[Abstract]:Objective: to detect the common mutation sites of SLC26A4 gene in sensorineural deaf-deaf population in Guangxi, and to analyze the characteristics of SLC26A4 common deafness gene mutation in Guangxi, so as to provide reference for clinical prevention and treatment of deafness. Methods: 90 deafness patients in 3 special education schools of Duan County, Fusui County and Wuming County, Guangxi, 43 patients who received cochlear implantation in our hospital and 40 patients who had not passed the hearing screening in outpatient clinic were studied. 137 patients with sudden deafness, a total of 310 patients with deafness. There were 194 males, 116 females, 167 Zhuang, 127 Han, 12 Yao, 2 Miao, 1 Dong, 1 Mulao, 170 prelingual deafness, 140 postverbal deafness, 31 sensorineural moderate deafness, 24 severe deafness, 255 extremely severe deafness. 44 patients with family history of deafness underwent unilateral cochlear implantation and 1 received bilateral cochlear implantation. All the subjects collected peripheral blood and extracted genomic DNA for PCR amplification, using the crystal core provided by Boo Biological Co., Ltd. Fifteen genetic deafness gene detection kits (microarray chip method) were used to detect 8 mutation sites of SLC26A4 in genomic DNA of the sample. The unconfirmed positive results were sequenced. Results 9 out of 1.310 cases had deafness gene mutation, the positive rate was 2.90% or 9 / 310%, among which 4 cases were heterozygous mutations of IVS7-2AG, 4 cases were 1.29% 31029CT homozygous mutation 1 case was 0.32% / 1231029CT heterozygous mutation 1 case was 0.321p / 1231010CT heterozygous mutation, 1 case was 0.32p-1 / 1310c26A4 1226GA complex heterozygous mutation 1 case was 0.32 / 1101011010V IVS7-2r-IVS11 47T?C/1548insC complex heterozygous mutation 2 cases were 0.652P / 231010 / 2. There were 4 cases of Han mutation, the positive rate was 3.15% and 4 / 127%, among them, 1 case of 1229CT heterozygous mutation was 0.79 / 127 CT homozygous mutation, 1 case was 0.79 / 127% IVS7-2AG heterozygous mutation, 2 cases (1.57%) were heterozygous mutation of IVS7-2AG. There were 5 cases of Zhuang mutation, the positive rate was 2.99% / 167%, of which 2 cases of IVS7-2AG heterozygosity mutation were 1.20% or 1.20%, and 2 cases of IVS7-2AGR / IVS11 47T?C/1548insC compound heterozygosity mutation 2 cases were 1.207-2AGR / IVS11 47T?C/1548insC complex heterozygosity mutation. One case of complex heterozygosity mutation of SLC26A4 1226GA was 0.601 / 167G. There was no significant difference between Zhuang and Han nationality. In 44 patients with family history of deafness, 3 of 44 patients with SLC26A4 gene mutation were found to be positive for SLC26A4 gene mutation. 4. SLC26A4 mutation was found in 3 out of 90 deaf school patients. 3 of 90 patients with hearing loss had a mutation of 3.33 / 90, 2 of 43 patients with cochlear implants had mutation of 4.65 / 43, 2 of them did not pass the screening of patients' mutation, and 2 of the patients with sudden deafness suffered from sudden deafness. No related gene mutations have been found. Conclusion 1. The detection rate of 8 common deafness loci in patients with sensorineural deafness in Guangxi was lower than the national average, mainly IVS7-2AG mutation loci. There was no significant difference in the mutation rate of common deafness gene between Zhuang nationality and Han nationality in Guangxi. The 47TC and 1548insC loci of IVS11 were two newly discovered mutation sites, and there might be rare mutation loci of deafness gene in Guangxi.
【学位授予单位】：广西中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R764.43

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