CAJ | 학술논문

目的探讨非综合征性耳聋的分子病机制,并在此基础上建立遗传性耳聋产前基因诊断方法.方法应用耳聋基因芯片和GJB2全编码序列分析对66个非综合征性耳聋家系的GJB2基因、SLC26A4基因和线粒体基因进行突变检测,并为7例高危孕妇提供产前基因诊断.结果在66例非综合征性耳聋患者中,两种方法共检测到GJB2基因突变携带者14例(21.21％,1例芯片未检测到),包括235delC纯合突变3例、176del16纯合突变2例、235delC/299delAT复合杂合突变2例、299delAT/176del16复合杂合突变1例、c.339T＞G/313 del12 bp复合杂合突变1例、235delC杂合突变5例.发现SLC26A4基因突变携带者13例(19.70％),包括2168A＞G纯合突变2例、IVS7-2A＞G纯合突变2例、2168A＞G/IVS7-2A＞G复合杂合突变3例、2168A＞G杂合突变3例、IVS7-2A＞G杂合突变3例.mtDNA12S rRNA基因突变3例(4.54％),包括1555A＞G均质突变2例、1494C＞T均质突变1例.7例高危胎儿中,3例分别为235delC、35insG和2168A＞G杂合突变携带者,2例未见突变,随访听力正常；1例为235delC/299delAT复合杂合突变,1例为235delC纯合突变.结论基因芯片结合GJB2序列分析是诊断非综合征性耳聋的一种准确和高效的方法.产前诊断可为遗传性耳聋家庭提供准确的遗传咨询.
목적 탐토비종합정성이롱적분자병궤제,병재차기출상건립유전성이롱산전기인진단방법.방법 응용이롱기인심편화GJB2전편마서렬분석대66개비종합정성이롱가계적GJB2기인、SLC26A4기인화선립체기인진행돌변검측,병위7례고위잉부제공산전기인진단.결과 재66례비종합정성이롱환자중,량충방법공검측도GJB2기인돌변휴대자14례(21.21％,1례심편미검측도),포괄235delC순합돌변3례、176del16순합돌변2례、235delC/299delAT복합잡합돌변2례、299delAT/176del16복합잡합돌변1례、c.339T＞G/313 del12 bp복합잡합돌변1례、235delC잡합돌변5례.발현SLC26A4기인돌변휴대자13례(19.70％),포괄2168A＞G순합돌변2례、IVS7-2A＞G순합돌변2례、2168A＞G/IVS7-2A＞G복합잡합돌변3례、2168A＞G잡합돌변3례、IVS7-2A＞G잡합돌변3례.mtDNA12S rRNA기인돌변3례(4.54％),포괄1555A＞G균질돌변2례、1494C＞T균질돌변1례.7례고위태인중,3례분별위235delC、35insG화2168A＞G잡합돌변휴대자,2례미견돌변,수방은력정상；1례위235delC/299delAT복합잡합돌변,1례위235delC순합돌변.결론 기인심편결합GJB2서렬분석시진단비종합정성이롱적일충준학화고효적방법.산전진단가위유전성이롱가정제공준학적유전자순.
Objective To detect genetic mutations underlying non-syndromic hearing impairment (NSHI) and establish a method for prenatal diagnosis.Methods Sixty-six NSHI patients were included in this study.DNA was extracted from peripheral blood.Gene mutations were analyzed by gene chip analysis and direct sequencing of GJB2 gene.For 7 pregnant women at high risk,prenatal gene diagnosis was provided.Results Fourteen cases (21.21％) were found to have GJB2 mutations by the two methods (homozygous 235delC mutation in 3 cases,homozygous 176del16 mutation in 2 cases,235delC and 299delAT compound heterozygous mutation in 2 cases,299delAT and 176del16 compound heterozygous mutation in 1 cases,c.339T＞G and 313del 12 bp compound heterozygous mutation 1 cases,and 235delC heterozygous mutation in 5 cases); 13 cases (19.70％) had SLC26A4 mutation (IVS7-2 A＞G homozygous mutation in 2 cases,IVS7-2 A＞G homozygous mutation in 2 cases,IVS7-2 A＞G and 2168A＞G compound heterozygous mutation in 3 cases,2168A＞G heterozygous mutation in 3 cases and IVS7-2 heterozygous mutation in 3 cases); and 3 had mtDNA12S rRNA mutation (1555A＞G mutation in 2 cases,1494C＞T mutation in 1 case).Prenatal diagnosis suggested that 3 fetuses have carried a heterozygous mutation.Two fetuses were detected as normal and were confirmed to have normal hearing after birth.Two fetuses were found to have carried compound mutations of GJB2.Conclusion Gene chip combined with GJB2 sequencing analysis is an accurate and effective method for the diagnosis of NSHI.The results can facilitate accurate prenatal diagnosis.