摘要
目的对1个常染色体隐性遗传性耳聋家系进行遗传性耳聋基因变异筛查。方法应用高通量测序技术(next generation sequencing,NGS)对家系先证者进行耳聋基因检测(包含139个已知致病基因,包括核基因、相关线粒体区域及miRNA),并对可疑位点行Sanger测序验证和家系验证。结果高通量测序提示先证者存在GJB2(gap junction protein,beta-2)基因c.235delC杂合变异,同时其OTOF基因存在c.1194T>A(p.D398E)和c.2180A>G(p.N727S)复合杂合变异;家系验证提示先证者妹妹(同为患者)存在GJB2基因c.235delC杂合变异,但OTOF基因仅存在c.2180A>G(p.N727S)杂合变异;Sanger测序发现家系两例患者GJB2基因的第1内含子区均存在IVS1+2T>A杂合变异,先证者及其妹妹均为GJB2基因c.235delC和IVS1+2T>A复合杂合变异患者。结论GJB2基因c.235delC和IVS1+2T>A复合杂合变异导致该家系遗传性耳聋的可能性大,IVS1+2T>A变异是GJB2基因新发现的致病性变异。
Objective To detect potential mutation in a pedigree affected with autosomal recessive non-syndromic deafness.Methods Mutation analysis was carried out by next generation sequencing,and suspected mutations were verified by Sanger sequencing.Results A heterozygous c.235delC mutation of the GJB2 gene,together with compound heterozygous mutations of the OTOF gene [c.1194T>A (p.D398E) and c.2180A>G (p.N727S)]were detected in the proband.The sister of the proband (also had hearing loss)has carried a heterozygous c.235delC mutation in the GJB2 gene,in addition with a heterozygous c.2180A>G (p.N727S)mutation of the OTOF gene.By Sanger sequencing,a heterozygous IVS1+2T>A mutation was further detected in the non-coding region of the GJB2 gene in both sisters.Conclusion The compound heterozygous c.235delC and IVS1 +2T>A mutations of the GJB2 gene probably account for the hearing loss in the two sisters,among which IVS1+2T>A is considered as a novel pathogenic mutation of the GJB2 gene.
作者
任淑敏
孔祥东
史惠蓉
Ren Shumin;Kong Xiangdong;Shi Huirong(The First Affiliated Hospital,Zhengzhou University,Zhengzhou,Henan 450000,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2018年第6期864-867,共4页
Chinese Journal of Medical Genetics
关键词
高通量测序
GJB2基因
耳聋
Next generation sequencing
GJB2 gene
Hearing loss
