南宁市1027例新生儿耳聋基因筛查结果分析

Analysis of Gene Screening Results in 1 027 Cases of Neonatal Deafness in Nanning

目的:探讨GJB2、GJB3、SLC26A4和线粒体12SrRNA四个耳聋基因在南宁市新生儿耳聋基因检测中的应用价值。方法:随机选取2016年1月-2018年12月南宁市新生儿疾病筛查中心1 027例新生儿足跟血滤纸片,并提取DNA,应用测序法检测耳聋基因突变位点,包括GJB2(c.35del G、c.176-191del16、c.235delC、c.299-300del AT、c.109G>A、c.11 G>A)、GJB3(c.538C>T)、SLC26A4(IVS 7-2A>G、c.2168A>G)和线粒体12SrRNA(1555A>G、1494C>T)共11个突变位点。结果:1 027例新生儿中检出耳聋基因的突变者183例,占17.82%,其中GJB2基因突变176例,占17.14%,其中纯合子突变23例(c.235del C 1例,c.109G>A 22例),占2.24%;杂合子突变153例(c.235del C 10例,c.299-300del AT 1例,c.109G>A 138例,c.11 G>A 4例),占14.90%。GJB3(c.538C>T)杂合子突变1例,占0.10%。SLC26A4(IVS 7-2A>G)杂合子突变3例,占0.29%。线粒体12SrRNA(1555A>G)均质突变3例,占0.29%。本地区的GJB2和SLC26A4突变率与济宁、东莞、珠海、绍兴的突变率比较,差异均有统计学意义(P<0.05)。结论:南宁市新生儿耳聋GJB2基因突变率比较高,GJB3、SLC26A4和线粒体12SrRNA基因突变率较低。致病基因以GJB2 c.109G>A为主,通过测序方法才能检测出基因突变位点比较多,有利于发现本区域的致病基因突变位点。

Objective:To explore the application value of GJB2,GJB3,SLC26A4 and mitochondrial 12SrRNA in the detection of deafness genes in newborn infants in Nanning.Method:1 027 cases of neonatal heel blood from nanning neonatal disease screening center from January 2016 to December 2018 were randomly selected.DNA was extracted and the deafness gene mutation site was detected by sequencing,including GJB2 (C.35del G,c.176-191del16,c.235delC,c.299-300del AT,c.109G>A,c.11G>A),GJB3 (C.538C>T),SLC26A4 (IVS7-2A>G,c.2168A>G) and mitochondrial 12SrRNA (1555A>G,1494C>T).Result:183 cases (17.82%) of 1 027 newborns were found to have hearing loss,among which 176 cases (17.14%) had mutation of GJB2 gene.Among them,there were 23 cases (c.235del C 1 case,c.109G>A 22 cases) homozygous mutations,accounting for 2.24%;153 cases (c.235 del C 10 cases,c.299-300del AT 1 case,c.109G>A 138 cases,c.11 G>A 4 cases) of heterozygous mutation accounted for 14.90%.1 case (0.10%) of heterozygous mutation in GJB3 (c.538C>T);SLC26A4(IVS 7-2A>G) heterozygous mutation was found in 3 cases (0.29%).Mitochondrial 12SrRNA 1555A>G homogeneous mutation was found in 3 cases (0.29%).The mutation rates of GJB2 and SLC26A4 in this region were statistically significant compared with those of Jining,Dongguan,Zhuhai and Shaoxing (P<0.05).Conclusion:The mutation rate of GJB2 gene in newborns with deafness in Nanning is higher,while that of GJB3,SLC26A4 and mitochondrial 12SrRNA is lower.GJB2 c.109G>A is the main pathogenic gene,only by sequencing method can there be many mutation sites,which is helpful to find the mutation site of the pathogenic gene in this region.