摘要
目的 了解江西地区耳聋患儿4个致聋基因9个常规筛查变异位点(GJB2基因的35delG、235delC、176del16bp、299-300delAT,SLC26A4基因的919-2A>G、2168 A>G,线粒体12S rRNA基因的1494C>T、1555A>G,GJB3基因的538C>T)以外的变异携带情况.方法 选取2018年1月1日—2021年9月30日江西省儿童医院耳聋基因筛查结果为阴性或仅携带GJB2和/或SLC26A4单一杂合变异的耳聋患儿118例.采用多重聚合酶链反应(PCR)扩增捕获技术检测耳聋基因数据库中GJB2、SLC26A4、12S rRNA基因所有已知的致病性位点,并分析变异位点的规律.结果 118例耳聋患儿中共检出其他变异位点19个,其中GJB2基因2个、SLC26A4基因16个、线粒体12S rRNA基因1个.有32例患儿检出GJB2基因c.109G>A位点变异,其中纯合子20例;检出GJB2 c.139G>T杂合突变1例.在检出的SLC26A4基因16个其他致病性变异位点中,c.1229C>T检出3次,c.916dup、c.1226G>A、c.1905G>A各检出2次,c.2T>G、c.84C>A、c.349del、c.757A>G、c.1079C>T、c.1174A>T、c.1286C>A、c.1692dup、c.1707+5G>A、c.1983C>A、c.2000T>C和c.2162C>T各检出1次.检出线粒体12S rRNA基因m.1027A>G变异位点携带者1例.结论 江西省耳聋患儿除9个常规筛查变异位点以外,以GJB2基因c.109 G>A变异位点检出率最高;SLC26A4基因其他变异位点检出数量多,且分布分散,c.1229C>T、c.1226G>A、c.916dup、c.1905G>A的检出率较高.多重PCR扩增捕获技术能有效提高耳聋患儿基因变异位点检出率.
Abstract
Objective To investigate the carrier status of hearing loss gene mutations beyond the 9 commonly screened variants(GJB2:35delG,235delC,176del16bp,299-300delAT;SLC26A4:919-2A>G,2168A>G;12S rRNA:1494C>T,1555A>G;GJB3:538C>T)among pediatric hearing loss patients in Jiangxi,China.Methods A total of 118 pediatric patients diagnosed with hearing impairment at Jiangxi Provincial Children's Hospital between January 1,2018 and September 30,2021 were screened.Patients who tested negative for the 9 variants or carried a single heterozygous mutation in GJB2 and/or SLC26A4 were included.Multiplex polymerase chain reaction(PCR)amplification and capture techniques were employed to detect all known pathogenic variants in GJB2,SLC26A4 and 12S rRNA genes.Variant patterns were analyzed.Results Totally,19 additional variants were detected among 118 patients,including 2 in the GJB2 gene,16 in the SLC26A4 gene,and 1 in the 12S rRNA gene.Among these patients,32 cases exhibited the GJB2 c.109G>A variant,with 20 in homozygous form.Additionally,one presented with the GJB2 c.139G>T heterozygous variant.Among the 16 other pathogenic variants detected in the SLC26A4 gene,the c.1229C>T variant appeared 3 times,while c.916dup,c.1226G>A and c.1905G>A were detected twice.The remaining variants(c.2T>G,c.84C>A,c.349del,c.757A>G,c.1079C>T,c.1174A>T,c.1286C>A,c.1692dup,c.1707+5G>A,c.1983C>A,c.2000T>C and c.2162C>T)were identified once.One case carried the m.1027A>G variant in the mitochondrial 12S rRNA gene.Conclusions In addition to the 9 commonly screened mutations,the GJB2 c.109G>A variant shows the highest detection rate in pediatric hearing impairment patients in Jiangxi.A diverse range of additional SLC26A4 gene variants is identified,with c.1229C>T,c.1226G>A,c.916dup and c.1905G>A occurring at relatively high frequencies and warranting further attention.The use of multiplex PCR amplification and capture techniques significantly improves the detection rate of gene variants in pediatric hearing impairment patients.
维普
万方数据