基因芯片联合测序技术在新生儿耳聋基因筛查中的应用

Application of Gene Chip combined Sequencing Technology in Newborn Deafness Screening

目的明确基因芯片在本地区初筛的准确性,分析本地区新生儿耳聋基因突变率及突变类型,为本地区的耳聋基因筛查工作提供理论依据。方法本研究选取2019年8月至2020年4月在我院出生的新生儿作为研究对象,并进行4个耳聋基因15个突变位点[GJB2(c.35delG,c.176191del16,c.235delC,c.299300delAT),SLC26A4(c.IVS7-2A>G,c.2168A>G,c.1174A>T,c.1226G>A,c.IVS15+5G>A,c.1975G>C,c.2027T>A,c.1229C>T)GJB3(c.538C>T),mt 12SrRNA(m.1555A>G、m.1494C>T)]基因芯片筛查,阳性位点同时进行测序验证。结果基因芯片与测序法检测基因突变一致性为99.8%;宁波地区新生儿耳聋基因总体突变率为5.47%,常见突变类型为GJB2基因235delC杂合突变和SLC26A4 IVS7-2A>G杂合突变;与中国其他地区比较突变率略高。结论基因芯片筛查联合测序技术可以准确检出耳聋基因突变情况,有助于早期发现与遗传相关的迟发性耳聋和药物性耳聋。

Objective:To clarify the accuracy of gene screening and to analyze the mutation rate and mutation types of deafness gene among newborns in the region providing theoretical basis for deafness gene screening in this region.Methods:The study included 1372 babies born in our hospital from August 2019 to April 2020.All subjects underwent newborn deafness genetic screening covering 15 variants in 4 genes,i.e.the GJB2 gene(c.35delG,c.176191del16,c.235delC,c.299300delAT),SLC26A4 gene(c.IVS7-2A>G,c.2168A>G,c.1174A>T,c.1226G>A,c.IVS15+5G>A,c.1975G>C,c.2027T>A,c.1229C>T),Mt12S rRNA(m.1555A>G,m.1494C>T)and GJB3 gene(c.538C>T).The positive sites were simultaneously verified by sequencing.Results:The alignment of microarray and sequencing method to detect the mutations is 99.8%.The total mutation rate of neonatal deafness gene in Ningbo was 5.47%,slightly higher than the average mutation rate(4.02%)collected in other cities in China,And the most common mutation type was c.35delG heterozygous mutation in GJB2 gene,followed by SLC26A4 IVS7-2A>G heterozygous mutation.Conclusion:The gene chip screening combined sequencing technology can accurately detect the genetic mutation of deafness,which is helpful for the early detection of genetic related delayed deafness and drug deafness.