CAJ | 학술논문

目的为仅检出1个致病等位基因的两个眼皮肤白化病(oculocutaneous albinism,OCA)的核心家系进行分型并提供产前基因诊断.方法应用DNA测序法检测先证者的TYR、P、TYRP1和SLC45A2 4个OCA基因,结合临床表型特点判定其OCA类型,在此基础上运用突变位点检测结合致病基因内单核苷酸多态位点家系连锁分析法进行产前基因诊断.结果家系1先证者仅在P基因检出c.1255C＞T杂合性致病突变,该突变来自母亲,结合临床表型特征综合分析判定先证者为OCA2患者.羊水筛查未见致病突变,家系连锁分析结果提示胎儿为OCA2携带者,出生时表型正常;家系2先证者仅在P基因检出c.1920_1949 del30bp和ins AACA杂合性致病突变,该突变来自父亲,结合临床表型特征综合分析判定先证者为OCA2患者.羊水筛查检出c.1920_1949 del30bp和ins AACA杂合突变,家系连锁分析结果提示胎儿为OCA2携带者,出生时表型正常.结论首次成功应用突变直接检测联合单核苷酸多态位点家系连锁分析法完成只检出1个致病突变的家系的OCA产前诊断.
목적 위부검출1개치병등위기인적량개안피부백화병(oculocutaneous albinism,OCA)적핵심가계진행분형병제공산전기인진단.방법 응용DNA측서법검측선증자적TYR、P、TYRP1화SLC45A2 4개OCA기인,결합림상표형특점판정기OCA류형,재차기출상운용돌변위점검측결합치병기인내단핵감산다태위점가계련쇄분석법진행산전기인진단.결과 가계1선증자부재P기인검출c.1255C＞T잡합성치병돌변,해돌변래자모친,결합림상표형특정종합분석판정선증자위OCA2환자.양수사사미견치병돌변,가계련쇄분석결과제시태인위OCA2휴대자,출생시표형정상;가계2선증자부재P기인검출c.1920_1949 del30bp화ins AACA잡합성치병돌변,해돌변래자부친,결합림상표형특정종합분석판정선증자위OCA2환자.양수사사검출c.1920_1949 del30bp화ins AACA잡합돌변,가계련쇄분석결과제시태인위OCA2휴대자,출생시표형정상.결론 수차성공응용돌변직접검측연합단핵감산다태위점가계련쇄분석법완성지검출1개치병돌변적가계적OCA산전진단.
Objective To provide prenatal diagnosis for two families affected with oculocutaneous albinism (OCA),in both of which only 1 pathogenic allele has been identified.Methods To determine the clinical classification of OCA through DNA sequencing for TYR,P,TYRP1 and SLC45A2 genes in combination with phenotype analysis.Prenatal diagnosis was carried out by direct sequencing and intragenic SNPs family-based linkage analysis.Results In the first family,only 1 heterozygous mutation c.1255C＞T was found in the proband,which was inherited from her mother.Together with its clinical phenotype,the proband was suspected to have OCA2.Screening of amniotic fluid,however,has found no mutation.With family-based linkage analysis,the fetus was deemed to be an OCA2 carrier.In the second family,again only one heterozygous mutation c.1920_1949 del30bp and ins AACA was found in the proband,which was inherited from her father.Together with its clinical phenotype,the proband was suspected to have OCA2.Screening of amniotic fluid has revealed a heterozygous mutation c.1920_1949 del30bp and ins AACA.By family-based linkage analysis,the fetus was deemed to be an OCA2 carrier.Both fetuses had a normal phenotype at birth.Conclusion Prenatal genetic diagnosis has been provided for the first time for two families affected with OCA,in which only 1 pathogenic mutant allele was detected.The combined mutation detection and SNPs linkage analysis has turned out to be successful.