摘要
目的分析深圳地区非综合征型耳聋患者及其相关高危人群中常见耳聋基因变异位点的分布,为分子诊断、遗传咨询及流行病学研究提供依据。方法应用基质辅助激光解析电离飞行质谱方法,对深圳地区1~6岁语前聋患儿71例及其听力正常的家庭成员(耳聋高危人群)145例,和作为对照听力的正常人群200例进行GJB2、SLC26A4、GJB3及MT-RNR1基因的20个变异位点的检测。结果常见耳聋基因热点变异的检出率在语前聋患儿中为37%(26/71),在高危人群中为28%(40/145),在正常健康人群中为4.5%(9/200);GJB2热点变异检出率在语前聋患儿中为18%(13/71),在高危人群中为12%(17/145),在正常人群中为2%(4/200);SLC26A4检出率在语前聋患儿中为18%(13/71),在高危人群中为16%(23/145),在正常人群中为2.5%(5/200)。语前聋患儿组和耳聋高危人群组之间GJB2和SLC26A4变异检出率没有统计学意义(P=0.209),但两者都显著比正常人群高(P均<0.0001);语前聋患儿中GJB2和SLC26A4变异纯合子和复合杂合子占18%(13/71),耳聋高危人群和正常人群中均未发现纯合子和复合杂合子,与语前聋患儿组比较有统计学意义(P<0.0001)。GJB3和MT-RNR1变异在语前聋患儿、高危人群和正常人群中均未发现。结论GJB2和SLC26A4纯合和复合杂合变异是深圳地区语前聋患儿的重要致病原因,其中最常见的变异位点是GJB2:c.235delC和SLC26A4:c.919-2A>G。对于仅检出单杂合变异的耳聋患儿,可进行相应基因的测序,进一步明确分子诊断。
Objective To analyze the distribution of common pathogenic variants for hearing loss in children with nonsyndromic hearing loss and relevant high risk population in Shenzhen so as to provide evidence for molecular diagnosis,genetic counseling and epidemiologic study.MethodsMatrix-assisted laser desorption ionization time of flight mass spectrometry（MALDI-TOF-MS）technology was used to detect twenty genetic variants in GJB2,GJB3,SLC26A4,and MT-RNR1 in 71 children with pre-lingual hearing loss aged one to six years（hearing loss group）,145 hearing family members as the high-risk population（high-risk group）,and 200 irrelevant individuals with normal hearing as controls（control group）.Results Common pathogenic variants for hearing loss were detected in 37%（26/71）of children in the hearing loss group,28%（40/145）of the high-risk group,and 4.5%（9/200）of the control group.The detection rates of GJB2 variants were 18%（13/71）of children in the hearing loss group,12%（17/145）of the high-risk group,and 2%（4/200）of the control group,while those of SLC26A4 variants were 18%（13/71）,16%（23/145）,and 2.5%（5/200）respectively.The detection rates of GJB2 and SLC26A4 in both the hearing loss group and high-risk group were markedly higher than those in the control group（all P〈0.0001）,while their differences between the hearing loss group and high-risk group were statistically insignificant（P=0.209）.GJB2 and SLC26A4 homozygotes and compound heterozygotes constituted 18%（13/71）of children in the hearing loss group.Homozygotes and compound heterozygotes were not detected in the high-risk population or in controls,which was statistically different from children of the hearing loss group（P〈0.0001）.GJB3 and MT-RNR1 variants were not found in any individuals tested.Conclusions Homozygosity and compound heterozygosity of common pathogenic variants in GJB2 and SLC26A4 are significant causes of the pre-lingual hearing loss in Shenzhen,and GJB2：c.235delC and SLC26A4：c.919-2AG are the most frequently detected variants.If only one heterozygous pathogenic variant is detected in a child with hearing loss,full gene sequencing should be recommended to establish the molecular etiology.
作者
柴福
马世博
沈珺
CHAI Fu;MA Shi-bo;SHEN Jun(Department of Otolaryngology,Longgang ENT Hospital,ENT Institute of Shenzhen City,Shenzhen 518172,China;Department of Pathology,Brigham and Women＆ Hospital,Harvard Medical School,Boston MA 02115,USA)
出处
《中国耳鼻咽喉颅底外科杂志》
CAS
2018年第5期459-464,共6页
Chinese Journal of Otorhinolaryngology-skull Base Surgery
基金
深圳市科技计划项目(JCYJ20170302165836389)
关键词
非综合征型听力损失
变异
遗传
基因
Non-syndromic hearing loss （NSHL）
Variation
Inheritance
Gene
