CAJ | 학술논문

目的对两个X连锁隐性遗传少汗性外胚层发育不良(X-linked hypohidrotic ectodermal dysplasia,XLHED)家系进行ED1基因突变分析,为罹患家庭提供遗传咨询及产前诊断.方法综合应用序列分析及多重连接依赖性探针扩增方法,对两个家系的先证者进行ED1基因突变分析,并针对检测到的突变位点对女性成员进行检测.采集家系1胎儿的羊水细胞进行产前诊断,包括致病突变位点的分析、ED1基因内4个短串联重复序列(short tandem repeat,STR)位点的单倍型连锁分析、性别鉴定及核型分析.结果家系1先证者缺失ED1基因第1外显子及下游2个STR位点DXS8269,DXS1422区域,其余外显子序列分析未见异常,其女儿为该缺失突变的携带者；结合连锁分析、性别鉴定及核型分析结果,家系1胎儿为男性非ED1基因缺失突变携带者,胎儿足月分娩后随访,为健康个体.家系2先证者经序列分析检测到ED1基因第3外显子c.463C＞T(R155C)错义突变,母亲为c.463C＞T(R155C)杂合突变携带者.结论 ED1基因第1外显子区域缺失和错义突变R155C是导致2个少汗性外胚层发育不全家系患者临床表型的主要原因,ED1基因的突变检测结合单倍型分析,能准确地对该类家系提供产前诊断.
목적 대량개X련쇄은성유전소한성외배층발육불량(X-linked hypohidrotic ectodermal dysplasia,XLHED)가계진행ED1기인돌변분석,위리환가정제공유전자순급산전진단.방법 종합응용서렬분석급다중련접의뢰성탐침확증방법,대량개가계적선증자진행ED1기인돌변분석,병침대검측도적돌변위점대녀성성원진행검측.채집가계1태인적양수세포진행산전진단,포괄치병돌변위점적분석、ED1기인내4개단천련중복서렬(short tandem repeat,STR)위점적단배형련쇄분석、성별감정급핵형분석.결과 가계1선증자결실ED1기인제1외현자급하유2개STR위점DXS8269,DXS1422구역,기여외현자서렬분석미견이상,기녀인위해결실돌변적휴대자；결합련쇄분석、성별감정급핵형분석결과,가계1태인위남성비ED1기인결실돌변휴대자,태인족월분면후수방,위건강개체.가계2선증자경서렬분석검측도ED1기인제3외현자c.463C＞T(R155C)착의돌변,모친위c.463C＞T(R155C)잡합돌변휴대자.결론 ED1기인제1외현자구역결실화착의돌변R155C시도치2개소한성외배층발육불전가계환자림상표형적주요원인,ED1기인적돌변검측결합단배형분석,능준학지대해류가계제공산전진단.
Objective To provide genetic diagnosis and counseling for patients from two families affected with X-linked hypohidrotic ectodermal dysplasia.Methods Potential mutation of the ED1 gene was screened by DNA sequencing.For family 1,multiplex ligation-dependent probe amplification (MLPA) analysis and haplotyping of ED1 gene were also carried out for prenatal diagnosis.Results For the patient from family 1,deletion of the exon 1 of the ED1 gene and 2 short tandem repeat(STR) sites (DXS8269 and DXS1422) were detected.His daughter was carrier of the deletion.Upon prenatal diagnosis,the fetus was confirmed to be a normal male,for whom the haplotype of ED1 gene has differed from that of the proband.In family 2,a c.463C＞T mutation in exon 3 of the ED1 gene was detected in the proband,whose mother was heterozygous for the same mutation.Conclusion The deletion (exon 1) and missense (R155C) mutation in ED1 gene have probably underlied the disease in the two families.During prenatal diagnosis,it may be necessary to obtain precise results through combining mutation detection and haplotype analysis of the ED1 gene.