新疆地区非综合征型聋患者耳聋相关基因检测结果分析

目的探讨新疆地区非综合征型耳聋患者常见耳聋基因突变热点,为该地区更好地开展耳聋基因诊断工作提供参考。方法通过问卷、健康体检及听力检测筛选出新疆地区399例非综合征型耳聋患者为研究对象,所有受检者均采集外周血并提取基因组DNA,应用分子生物学方法检测GJB2(c.35delG,c.167delT,c.176_191del16,c.235delC,c.299_300delAT)、SLC26A4(c.281C>T,c.589G>A,c.IVS7-2A>G,c.1174A>T,c.1226G>A,c.1229C>T,c.IVS15+5G>A,c.1975G>C,c.2027T>A,c.2162C>T,c.2168A>G)、mtDNA12SrRNA(c.1494C>T,c.1555A>G,c.1585A>G,c.1047A>G,c.1095T>C,c.960_961insC/c.961delT)基因22个位点突变情况。结果399例非综合征型耳聋患者中GJB2、SLC26A4、mtDAN12SrRNA基因的突变携带率分别为11.28%(45/399)、10.78%(43/399)、4.76%(19/399),致病突变率分别为6.52%(26/399)、3.76%(15/399)、3.51%(14/399)。c.235delC和c.IVS7-2A>G在汉族(16/92,11/92)和维吾尔族(18/273,10/273)中都是突变热点,在汉族中c.2168A>G也呈现突变热点趋势,而在维吾尔族中c.1174A>T、c.35delG、c.2027T>A等多个位点都呈现出突变热点的趋势。在汉族c.235delC(χ^2=9.498,P=0.002)、c.IVS7-2A>G(χ^2=8.729,P=0.003)和c.2168 A>G(P=0.001)突变率高于维吾尔族。结论GJB2、SLC26A4、mtDNA12SrRNA为新疆非综合征型耳聋常见致病基因,c.235delC和c.IVS7-2A>G是汉族和维吾尔族突变热点,汉族中c.235delC、c.IVS7-2A>G和c.2168A>G突变率显著高于维吾尔族。

Analysis of the Results of Deafness Gene Test in Non-syndrome Deafness Patients in Xinjiang

Objective To study the hotspots of common deafness gene mutation in patients with non-syndromic deafness in Xinjiang,and to provide theoretical basis for better diagnosis of deafness gene in this region.Methods A total of 399 cases of non-syndrome deafness in Xinjiang were screened out through questionnaire,physical examination and audiology.Peripheral blood were collected from all subjects and genomic DNA were extracted.Genes GJB2(c.35delG,c.167delT,c.176_191del16,c.235delC,c.299_300delAT),SLC26A4(c.281C>T,c.589G>A,c.IVS7-2A>G,c.1174 A>T,c.1226 G>A,c.1229 C>T,c.IVS15+5G>A,c.1975 G>C,c.2027 T>A,c.2162 C>T,c.2168 A>G)and mitochondrial gene 12SrRNA(c.1494C>T,c.1555A>G,c.1585A>G,c.1047A>G,c.1095T>C,c.960_961insC/c.961delT)contains 22 sites were detected and analyzed by molecular biological method.Results In 399 cases of non-syndromic deafness,the mutation rates of GJB2,SLC26A4 and mt12SrRNA were 11.28%(45/399),10.78%(43/399)and 4.76%(19/399),respectively.The frequency of pathogenic mutation was 6.52%(26/399),3.76%(15/399)and 3.51%(14/399),respectively.c.235delC and c.IVS7-2A>G are mutation hotspots in Han(16/92,11/92)and Uygur(18/273,10/273).The c.2168 A>G also showed a mutation hotspot trend in the Han nationality,while the c.1174 A>T,c.35delG,c.2027 T>A sites showed mutation hotspot trend in the Uygur nationality.The c.235delC in GJB2(χ^2=9.498,P=0.002),c.IVS7-2A>G in SLC26A4(χ^2=8.729,P=0.003),and c.2168 A>G(P=0.001)had significant differences between Han and Uygur.Conclusion GJB2,SLC26A4 and mt12SrRNA are common pathogenic genes for non-syndrome deafness in Xinjiang.c.235delC and c.IVS7-2A>G are mutation hotspots of Han and Uygur,and the mutation rates of c.235delC,c.IVS7-2A>G and c.2168 A>G in Han are significantly higher than that of Uygur.