非综合征型耳聋患者遗传性耳聋基因突变位点分析及遗传咨询

Analysis of genetic deafness mutation loci and genetic counseling in non-syndromic deafness patients in Xi'an

目的调查西安市246例耳聋患者常见耳聋相关基因GJB2、SLC26A4、线粒体12SrRNA和GJB3,突变位点分布情况,为寻求适合该地区人群的遗传咨询模式做数据支持。方法通过微阵列芯片法,对西安地区246例非综合征型耳聋患者,进行4个常见遗传性耳聋基因9个热点筛查,在后续遗传咨询中,进一步实施家系调查,并针对性地进行GJB2、SLC26A4基因全外显子序列分析。结果246例耳聋患者中,基因突变检出率34.55%(85/246),其中,GJB2基因突变率17.48%(43/246),SLC26A4基因突变率14.23%(35/246),7例线粒体DNA 12SrRN A1555A>G均质突变,占比2.85%(7/246)。另外,家系调查结果显示GJB2、SLC26A4基因突变携带率48.72%(19/39)。最后,GJB2和SLC26A4基因全外显子序列分析,在GJB2基因上发现了额外的突变位点c.605ins46,c.79G>A,c.341A>G,c.257C>G,c.109G>A。结论西安市耳聋患者基因筛查应以GJB2、SLC26A4基因突变为主,另外,不可忽视全面家系调查及适时联合GJB2、SLC26A4基因全外显子序列分析在后续诊断、治疗、生活及婚育指导等个性化遗传咨询上的重要作用。

Objective To investigate the distribution of mutations of common deaf-related genes GJB2,SLC26A4,mitochondria 12SrRNA and GJB3 in 246 patients with deafness in xi'an and provide support for finding a genetic counseling model suitabling for the population in this region.Methods Microarray was used to screen 9 hotspots of four common genetic deafness genes in 246 patients with non-syndromic deafness in xi'an.In the follow-up genetic counseling,a further family investigation was conducted,and the complete exon sequence analysis of GJB2 and SLC26A4 genes was treated.Results Among 246 patients with deafness,the detection rate of gene mutation was 34.55%(85/246),including GJB2 gene mutation 17.48%(43/246),SLC26A4 gene mutation 14.23%(35/246),and mitochondrial DNA 12SrRN A1555A>G homogeneous mutation 2.85%(7/246).In addition,the results of family investigation showed that the mutation carrying rate of GJB2 and SLC26A4 gene was 48.72%(19/39).Finally,the complete exon sequence analysis of GJB2 and SLC26A4 genes revealed additional mutation loci on GJB2 genes,including c.605ins46,c.79G>A,c.341A>G,c.257C>G,and c.109G>A.Conclusion Gene screening of 246 patients with deafness in xi'an should be mainly based on mutations of GJB2 and SLC26A4 genes.In addition,it should not neglect the important role of comprehensive pedigree investigation and timely combined exon sequence analysis of GJB2 and SLC26A4 genes in personalized genetic counseling such as follow-up diagnosis,treatment,life and marriage and parenting guidance.