湖南郴州非综合征型聋患者GJB2、SLC26A4和线粒体DNA12SrRNA基因突变分析

目的探讨湖南郴州非综合征型聋患者的分子病因特点。方法采取湖南郴州154名非综合征型聋患者的外周血,提取DNA,采用基因芯片筛查GJB2、SLC26A4和线粒体DNA12SrRNA基因的热点突变,基因芯片法未确诊的样本则采用DNA测序法进一步检测。结果两种方法共在34例(22.08%,34/154)患者中检出7种GJB2基因突变,其中235delC(13.63%,21/154)发生率最高,其次是299delAT(9.09%,14/154);在8例伴有大前庭水管的患者中检测出7种SLC26A4基因突变,包括一种新突变Q696X;3例患者被检出线粒体DNA12SrRNA基因突变。结论湖南郴州非综合征型聋患者中GJB2、SLC26A4和线粒体DNA12SrRNA基因突变的发生率与中国大部分地区相似,Q696X为新发现的SLC26A4基因突变。

The Mutation Analysis of GJB2,SLC26A4 and mtDNA12SrRNA Gene in Patients with Nonsyndromic Sensorineural Hearing Loss in Chenzhou,Hunan Province

Objective To explore the molecular epidemiology and effective genetic diagnostic method for the patients with nonsyndromic sensorineural hearing loss(NSHL),we reported the results of genetic examination based on DNA Microarray combined with DNA sequencing in the patients from Chenzhou,Hunan province in China.Methods Genomic DNA extracted from 154 patients with NSHL from Chenzhou was subjected to allele-specific PCR and universal array to screen for hot spot mutations in the GJB2,SLC26A4 or mtDNA12SrRNA gene.The samples that could not be diagnosed with DNA microarray were subjected to PCR and sequenced to detect other mutations in GJB2 and SLC26A4 gene.Results The GJB2 mutation was detected in 22.08% of the patients with NSHL.Of the 7 mutations detected,the 235delC was the most prevalent,followed by 299delAT.7 SLC26A4 mutations,including a novel mutation(Q696X),were detected in 8 cases with enlarged vestibular aqueduct.3 cases were found to have mutations in mtDNA12SrRNA gene.Conclusion DNA microarray combined with direct sequencing analysis allow us to produce accurate outcome in the genetic examination on patients with NSHL.The genetic cause of NSHL cases in Chenzhou is similar to most of other populations in China.The novel SLC26A4 mutation may further our understanding of the cause for hereditary hearing loss.