CAJ | 학술논문

目的观察双(多)胞胎Wilson病家系的临床和基因突变特点.方法收集双(多)胞胎Wilson病家系的临床资料,留取其全血标本,提取基因组DNA,应用短串联重复(short tandem repeats,STR)分型判定双胞胎是否为同卵双生,用DNA测序法检测ATP7B基因各外显子的突变.结果 5个双胞胎家系的患者均符合Wilson病的诊断标准.STR分型提示4个家系为同卵双生,1个家系为异卵双生.3个双胞胎家系的患者均以肝症状起病,另外2个家系的患者以脑症状起病.在4个家系的患者中检出ATP7B基因的突变,均位于第8和(或)第13外显子,其中1个家系的患者同时携带第8外显子p.R778W杂合突变和第13外显子p.P992L纯合突变,其父母分别为p.R778W杂合突变和p.P992L杂合突变的携带者,因此该家系的患者发生了杂合丢失现象.有1个家系的2例患者及其父母亲各外显子均未检出突变.1个三胞胎家系中的1名女性成员为脑症状起病的Wilson病患者,1名男性为无症状的亚临床型Wilson病患者,另1例女性成员未患病,这3位成员及其母亲均检出第13外显子p.P992L杂合突变.结论本研究结果进一步证实了遗传因素在Wilson病发病中的主要作用.杂合丢失现象是除点突变外Wilson病的另一种发病机制.
목적 관찰쌍(다)포태Wilson병가계적림상화기인돌변특점.방법 수집쌍(다)포태Wilson병가계적림상자료,류취기전혈표본,제취기인조DNA,응용단천련중복(short tandem repeats,STR)분형판정쌍포태시부위동란쌍생,용DNA측서법검측ATP7B기인각외현자적돌변.결과 5개쌍포태가계적환자균부합Wilson병적진단표준.STR분형제시4개가계위동란쌍생,1개가계위이란쌍생.3개쌍포태가계적환자균이간증상기병,령외2개가계적환자이뇌증상기병.재4개가계적환자중검출ATP7B기인적돌변,균위우제8화(혹)제13외현자,기중1개가계적환자동시휴대제8외현자p.R778W잡합돌변화제13외현자p.P992L순합돌변,기부모분별위p.R778W잡합돌변화p.P992L잡합돌변적휴대자,인차해가계적환자발생료잡합주실현상.유1개가계적2례환자급기부모친각외현자균미검출돌변.1개삼포태가계중적1명녀성성원위뇌증상기병적Wilson병환자,1명남성위무증상적아림상형Wilson병환자,령1례녀성성원미환병,저3위성원급기모친균검출제13외현자p.P992L잡합돌변.결론 본연구결과진일보증실료유전인소재Wilson병발병중적주요작용.잡합주실현상시제점돌변외Wilson병적령일충발병궤제.
Objective To study the clinical and genetic characteristics of twins and siblings affected with Wilson's disease (WD).Methods Clinical data and blood samples were collected from the subjects after informed consent was obtained.Genomic DNA was extracted and potential mutations in the exons in ATP7B gene were detected with PCR-DNA sequencing.Short tandem repeat (STR) genotyping was performed to determine the zygosity of the twins.Results The 5 pairs of twins have all met the diagnostic criteria for WD.STR genotyping has confirmed that 4 pairs were monozygotic twins.3 pairs of twins had an onset with liver symptoms,the other 2 had an onset with brain symptoms.ATP7B gene mutations were detected in 4 pairs of twins,which have all located in exons 8 and 13.A heterozygous p.R778W mutation in exon 8 and homozygous p.P992L mutation in exon 13 were detected in all patients from one family,whose parents have carried a heterozygous p.R778W mutation and p.P992L heterozygous mutation,respectively,which suggested loss of heterozygosity (LOH).In one family,no mutation was detected in all exons of the ATP7B gene in the patients and their parents.For a triplet,one female was with definite WD and brain symptoms at the onset,one male had subclinical type with WD,whilst another female was completely normal.The triplets and their mother have all carried a p.P992L heterozygous mutation.Conclusion Above results have confirmed an important role for genetic factors in the pathogenesis of WD.In addition to point mutations,LOH is also involved in the pathogenesis for WD.