【摘要】 目的探讨新生儿常见聋病易感基因突变位点分布情况,为临床干预奠定基础。方法采用实时荧光聚合酶链反应(PCR)技术对11 121例新生儿进行常见聋病易感基因突变位点筛查,筛查位点为我国常见的3个致聋基因GJB2(c.235 delC、c.299-300 del AT)、线粒体DNA 12S rRNA(c.1494 C>T、c.1555 A>C)和SLC26A4(c.2168 A>G、c.ⅣS7-2 A>G)的6个突变位点;基因突变者进行测序验证及听力诊断。结果 11 121例新生儿中发生耳聋基因突变者517例,其中纯合突变39例、杂合突变469例、单基因复合杂合突变2例,双基因复合杂合突变7例,阳性率4.65%。基因突变包括:GJB2突变286例(包括2例c.235 del C杂合突变复合c.299-300 del AT杂合突变);线粒体DNA 12S rRNA基因突变189例;SLC26A4基因突变35例;双基因复合杂合突变7例,男婴耳聋基因突变阳性率显著高于女婴(x~2=8.653,P<0.01)。测序结果与PCR结果一致,517例基因突变新生儿中13例发生听力损伤,其中轻度6例,中度3例,极重度4例。结论 GJB2基因的c.235 del C位点突变率最高,其次为SLC26A4基因的c.ⅣS7-2A>G位点,线粒体DNA 12S rRNA基因的c.1494C>T位点突变极低,不属于本地区的致聋热点基因,且男女婴之间突变阳性率存在显著差异,为该地区耳聋基因筛查方向提供了重要依据。更多还原

【Abstract】 Objective To investigate the distribution of mutational sites of common deafness-related susceptibility genes in neonates so as to lay a foundation for clinical interventions.Methods A total of 11 121 cases of neonates were screened for mutational sites of deafnessrelated susceptibility genes by using real-time fluorescence quantitative polymerasechain reaction technology.Screened sites were six mutational sites at three common deafness-related genes in China.Those genes were GJB2(c.235 del C,c.299-300 del AT),mtDNA12SrRNA(c.l494C>T,c.1555 A>C) and SLC26A4(c.2168 A>G,c.IVS7-2 A > G).Gene sequencing and hearing diagnosis were performed for individuals with mutant genes.Results Among 11 121 neonates,517 cases were deafness-related mutant gene carriers,including 39 cases of homozygous mutations,469 cases of heterozygous mutations,2 cases of single-gene compound heterozygous mutations and 7 cases of double-gene compound heterozygous mutations.The positive rate was4.65%.Among517 cases of genetic mutations,286 cases of GJB2 mutations(including 2 cases of compound heterozygous mutations of c.235 del C and c.299-300 del AT),189 cases of mtDNA 12 S rRNA gene mutations,35 cases of SLC26A4 gene mutations and 7 cases of double-gene compound heterozygous mutations were included.The positive rate of deafness-related genetic mutations in females neonates was higher than that in males(x~2 = 8.653,P <0.01).The results of gene sequencing were consistent with PCR results.Among 517 cases of neonates with genetic mutations,13 cases suffered from hearing impairment,including 6 mild cases,3 moderate cases,and 4 extremely severe cases.Conclusion The mutation rate reaches its peak at the mutation site c.235 del C of gene GJB2,followed by c.IVS7-2A > G of gene SLC26A4.However,the mutation rate is extremely low at the mutation site c.1494 C > T of mtDNA 12 S rRNA,indicating that it is not a hot-spot deafness-related gene in this area.In addition,there is significant difference in positive rate of mutation between female and male neonates.The preceding results have provided important evidences for directing the screening of deafness-related genes in this area.更多还原