新疆维汉两民族NSHI患者GJB2、GJB3及12S rRNA基因突变研究
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摘要
目的:研究新疆地区维吾尔族遗传性非综合征性耳聋人群中GJB2、GJB3、12S rRNA基因突变位点、突变频率及二者与汉族耳聋人群的差异。方法:对93例新疆地区遗传性非综合征性耳聋患者进行耳聋病因问卷调查、纯音听阈测试,另选取110名正常人作为对照组。其中病例组中有维吾尔族43例,汉族50例;对照组维吾尔族56例,汉族54例。收集血样提取DNA后经聚合酶链反应扩增, GJB2、GJB3两基因PCR产物直接测序。针对线粒体DNA 12S rRNAA1555G点突变进行限制性内切酶的分析。挑选阳性送测序。统计结果进行生物信息学分析。结果:93名患者检测到的GJB2基因变异共有4种,其中235delC共3例,另一种错义突变109G>A杂合突变共2例,多态性380G>A共2例。GJB3基因33C > T2例、766G > A 1例和357C > T7例,798C > T4例。8例患者存在12S rRNA A1555G突变, 2例维吾尔族6例汉族。对照组中检测到GJB2基因2种碱基改变多态性79G>A有1例,34lA>G共6例。GJB3基因357C > T4例,798C > T5例,93C > T有2例。比较GJB3基因798C > T在新疆两个不同民族中的分布,结果发现其分布在维吾尔族与汉族群体中的差异有统计学意义(P<0.05)。12S rRNA基因A1555G突变在汉族病例组和正常对照组中差异均有统计学意义(P<0.05)。结论:本文通过对新疆维吾尔族、汉族耳聋患者GJB2、GJB3、12S rRNA1555G位点基因突变的调查研究。GJB3基因798C > T在新疆两民族人群中的分布差异有统计学意义,推断该基因多态的分布具有民族特异性,可能与两民族不同发病特点有关。我们发现12S rRNA A1555G突变形式对于导致汉族遗传性非综合征耳聋有差异,可以初步认为该突变与汉族遗传性非综合征性耳聋有关。另外,在维吾尔族散遗传性非综合征耳聋人群中发现一个新的突变形式766G > A。
Objective :To investigate and determine the mutation situs and refrequency of GJB2、GJB3、mtDNA A1555G in Uygur people with hereditary nonsyndromic hearing loss,and to contrast the difference of the mutation situs and refrequency between Uygur and Han people. Methods:Blood samples were obtained from 93 patients(50 cases of Han) with hereditary non-syndromic deafness and 110 normal people(54 cases of Han) were selected as control group. Genomic DNA was extracted from the isolated leukocytes,Screening the mitochondrial A1555G mutation by PCR-Alw26I digestion and sequence analysis, PCR and direct sequencing were used to analyze the coding region of GJB2、GJB3 gene. Results:The sequencing resμlts revealed that four types of variants of GJB2 gene were detected. 3 patients carried GJB2 235delC heterozygous mutation, 2 patients carried heterozygosis base pair changes :109G>A. 2 cases carried 380G>A.Of GJB3 2 cases carried 33C > T , 2 cases carried 766G > A, 7 cases carried 357 C> T and 4 cases carried 357 C> T,8 patients were found to carry mt DNA A1555G mutation.In control group two types of variant s of GJB2 gene were detected. One case carried 79G>A , 6 cases carried 34lA>G .In GJB3 4 cases were found to have 357C > T mution ,5 cases carried 798C > T,2 cases carried 93C > T. Compare with 798C > T distribution in two ethnic and there were significantly different in Uygur and Han populations(P<0.05). 12S rRNA A1555G mutation was significant between case and control group in Han People(P<0.05).
Conclusion:798C > T mutation of GJB3 was significantly different in Uygur and Han populations,we indicated 798C > T mutation have ethnic specificity. 12S rRNA A1555G mutation had mutation rate with hereditary nonsyndramic hearing loss in Han people.So we considered it was significantly related with hereditary nonsyndramic hearing loss in Han people in Xinjiang.Addtion, a new mutation position(766G > A)was found in Uygur people with sporadic congenital deafness.
Objective :To investigate and determine the mutation situs and refrequency of GJB2、GJB3、mtDNA A1555G in Uygur people with hereditary nonsyndromic hearing loss,and to contrast the difference of the mutation situs and refrequency between Uygur and Han people. Methods:Blood samples were obtained from 93 patients(50 cases of Han) with hereditary non-syndromic deafness and 110 normal people(54 cases of Han) were selected as control group. Genomic DNA was extracted from the isolated leukocytes,Screening the mitochondrial A1555G mutation by PCR-Alw26I digestion and sequence analysis, PCR and direct sequencing were used to analyze the coding region of GJB2、GJB3 gene. Results:The sequencing resμlts revealed that four types of variants of GJB2 gene were detected. 3 patients carried GJB2 235delC heterozygous mutation, 2 patients carried heterozygosis base pair changes :109G>A. 2 cases carried 380G>A.Of GJB3 2 cases carried 33C > T , 2 cases carried 766G > A, 7 cases carried 357 C> T and 4 cases carried 357 C> T,8 patients were found to carry mt DNA A1555G mutation.In control group two types of variant s of GJB2 gene were detected. One case carried 79G>A , 6 cases carried 34lA>G .In GJB3 4 cases were found to have 357C > T mution ,5 cases carried 798C > T,2 cases carried 93C > T. Compare with 798C > T distribution in two ethnic and there were significantly different in Uygur and Han populations(P<0.05). 12S rRNA A1555G mutation was significant between case and control group in Han People(P<0.05).
Conclusion:798C > T mutation of GJB3 was significantly different in Uygur and Han populations,we indicated 798C > T mutation have ethnic specificity. 12S rRNA A1555G mutation had mutation rate with hereditary nonsyndramic hearing loss in Han people.So we considered it was significantly related with hereditary nonsyndramic hearing loss in Han people in Xinjiang.Addtion, a new mutation position(766G > A)was found in Uygur people with sporadic congenital deafness.
引文
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