中国东北地区非综合征性耳聋患者GJB2基因的致聋突变分析

目的分析58例中国东北地区非综合征性耳聋（nonsyndromic hearing impairment，NSm）患儿GJB2基因突变类型和频率。方法收集吉林省吉林市聋哑学校的58例非综合征性耳聋患儿（分别来自57个家庭）及37例听力正常家属的血样，经聚合酶链反应（Dolymerase chain reaction，PCR）扩增GJB2基因编码区。用酶切方法初步分析已知的233—235位点，进一步行DNA测序证实酶切结果并发现新的突变类型；同时对部分家属进行DNA测序，区分并证实致病突变位点或多态性改变。结果58例患儿中发现11例（18．97％）为233—235delC突变，其中7例（12．07％）为233—235delC纯合突变，4例（6．90％）为233—235delC杂合突变；发现1例35delG杂合突变；4例235delC杂合突变及1例35delG杂合突变者均伴有299—300delAT杂合突变。在患儿及听力正常的家属中均发现有G79A杂合及A341G杂合复合变异、G79A纯合及A341G纯合复合变异。结论东北地区NSHI患儿的GJB2突变热点为233—235delC，突变率为18．97％。233—235delC杂合及299—300delAT杂合复合突变、35delG杂合及299—300delAT杂合复合突变为致病突变。G79A杂合及A341G杂合复合变异、G79A纯合及A341G纯合复合变异为多态性改变。

Mutation analysis of GJB2 gene in nonsyndromic hearing impairment patients from Northeastern China

Objective To determine the prevalence and types of GJB2 gene mutation nonsyndromic hearing impairment patients from Northeastern China.Methods Subjects include 58 students from the Deaf and Mute School of Jilin city and 37 family members of some students.The peripheral blood samples were obtained and DNA templates were extracted by extraction kits.Using polymerase chain reaction(PCR),the code region of GJB2 gene was amplified.The mutations were detected by restriction endonuclease and direct sequence.Results GJB2 235delC was found in 11 cases(7 cases are homozygosis,4 cases are heterozygosis);35delG heterozygosis was found in 1 case.Heterozygous deletion AT at position 299-300 was found in all 235delC and 35delG heterozygosis cases.G79A heterozygosis compounded with A341G heterozygosis and G79A homozygosis compounded with A341G homozygosis were found in deafness students and their family members with normal hearing.Conclusion The hot spot of GJB2 mutation in Northeast nonsyndromic hearing impairment patients is 235delC,the incidence rate is 18.97%.235delC heterozygosis compounded with 299-300delAT heterozygosis,35delG heterozygosis compounded with 299-300delAT heterozygosis are also pathogenic deaf mutations in this group;G79A heterozygosis compounded with A341G heterozygosis and G79A homozygosis compounded with A341G homozygosis are polymorphism.