CAJ | 학술논문

目的研究一个毛囊闭锁三联征家系的临床特征及其致病基因的突变类型.方法依据确诊的毛囊闭锁三联征先证者对该家系进行现场调查,并采集外周血标本.运用PCR扩增早老素1(PSEN1)、单过性跨膜蛋白(NCSTN)和早老素增强子2(PSENEN)的所有外显子,经测序与比对后鉴定致病基因突变位点和突变方式.结果该家系共有3代14人,其中6人患病(男4例,女2例),符合常染色体显性遗传模式.对4例现存患者临床特征比较分析表明,患者临床表型差异显著.对3个基因的DNA测序分析发现,NCSTN基因6号外显子存在c.647A＞ C(p.Q216P)错义突变,且在该家系中基因型与表型呈完全共分离现象.同时检测100名健康对照,未发现该突变.检索美国国家生物技术信息中心(NCBI)网站单核苷酸多态性(SNP)数据库,未发现该突变.结论该家系存在一个新的错义突变,即NCSTN基因6号外显子c.647A＞C,这可能是该家系患者发病的分子基础.
목적 연구일개모낭폐쇄삼련정가계적림상특정급기치병기인적돌변류형.방법 의거학진적모낭폐쇄삼련정선증자대해가계진행현장조사,병채집외주혈표본.운용PCR확증조로소1(PSEN1)、단과성과막단백(NCSTN)화조로소증강자2(PSENEN)적소유외현자,경측서여비대후감정치병기인돌변위점화돌변방식.결과 해가계공유3대14인,기중6인환병(남4례,녀2례),부합상염색체현성유전모식.대4례현존환자림상특정비교분석표명,환자림상표형차이현저.대3개기인적DNA측서분석발현,NCSTN기인6호외현자존재c.647A＞ C(p.Q216P)착의돌변,차재해가계중기인형여표형정완전공분리현상.동시검측100명건강대조,미발현해돌변.검색미국국가생물기술신식중심(NCBI)망참단핵감산다태성(SNP)수거고,미발현해돌변.결론 해가계존재일개신적착의돌변,즉NCSTN기인6호외현자c.647A＞C,저가능시해가계환자발병적분자기출.
Objective To observe the clinical features and to identify γ-secretase gene mutations in a Chinese family with follicular occlusion triad (FOT).Methods Clinical evaluation was carried out in a family with FOT through field investigation.Peripheral blood samples were obtained from the family members and 100 unrelated healthy controls.DNA was extracted from the blood samples,and PCR was performed to amplify all the coding regions of PSEN1,PSENEN and NCSTN genes followed by DNA sequencing and comparative analysis.Results There were 14 members over 3 generations in this family,of whom,6 (4 males and 2 females) were affected by FOT.FOT was inherited in an autosomal dominant manner in this family.Clinical manifestations varied greatly among the 4 surviving affected members.DNA sequencing revealed a novel missense mutation,c.647A ＞ C (p.Q216P),in the exon 6 of NCSTN gene in the proband,which was cosegregated perfectly with affected,but not with unaffected,members in the family.The mutation was not found in any of the unrelated controls and had not been registered in the single nucleotide polymorphism (SNP) database in NCBI.Conclusions There is a novel heterozygous missense mutation,c.647A＞C in the exon 6 of NCSTN gene,which may be the molecular basis of pathogenesis of FOT in this family.