CAJ | 학술논문

目的分析遗传性出血性毛细血管扩张症(hereditary hemorrhagic telangiectasia,HHT)家系ENG、ACVEL1和SMAD4基因突变.方法收集4个HHT家系临床资料并分析其临床特点,应用直接测序和多重连接探针扩增技术对11例临床确诊及可疑患者的ENG、ACVRL1和SMAD4基因进行突变分析,将结果与HHT基因突变数据库进行对比.结果家系2先证者及2个妹妹的ENG基因发生了第2外显子c.207G＞A(p.L69L)同义突变、第8外显子c.1004A＞T(p.Q335L)错义突变、ACVRL1基因第7外显子c.817C＞T(L273L)同义突变；家系3先证者及其母亲和弟的ENG基因发生了第8外显子c.1004A＞T(p.Q335L)突变；也检测到家系4先证者及其兄的ENG基因第8外显子c.1004A＞T(p.Q335L)突变.家系1先证者及其他HHT患者,未检测到基因突变.其中ENG基因第8外显子c.1004A＞ T(p.335Q＞L)为新突变,在200名正常对照中也未检测到该突变.结论 HHT具有遗传异质性,ENG基因第8外显子c.1004A＞T(p.Q335L)为HHT新的致病突变.
목적 분석유전성출혈성모세혈관확장증(hereditary hemorrhagic telangiectasia,HHT)가계ENG、ACVEL1화SMAD4기인돌변.방법 수집4개HHT가계림상자료병분석기림상특점,응용직접측서화다중련접탐침확증기술대11례림상학진급가의환자적ENG、ACVRL1화SMAD4기인진행돌변분석,장결과여HHT기인돌변수거고진행대비.결과 가계2선증자급2개매매적ENG기인발생료제2외현자c.207G＞A(p.L69L)동의돌변、제8외현자c.1004A＞T(p.Q335L)착의돌변、ACVRL1기인제7외현자c.817C＞T(L273L)동의돌변；가계3선증자급기모친화제적ENG기인발생료제8외현자c.1004A＞T(p.Q335L)돌변；야검측도가계4선증자급기형적ENG기인제8외현자c.1004A＞T(p.Q335L)돌변.가계1선증자급기타HHT환자,미검측도기인돌변.기중ENG기인제8외현자c.1004A＞ T(p.335Q＞L)위신돌변,재200명정상대조중야미검측도해돌변.결론 HHT구유유전이질성,ENG기인제8외현자c.1004A＞T(p.Q335L)위HHT신적치병돌변.
Objective To analyze clinical features of 4 families with hereditary hemorrhagic telangiectasia (HHT) and potential mutations of ENG,ACVRL1 and SMAD4 genes.Methods Four unrelated HHT patients and their affected family members were analyzed.All exons and flanking regions of ENG,ACVRL1 and SMAD4 genes were analyzed with PCR and direct sequencing and multiplex ligationdependent probe amplification (MLPA) methods.Results Eleven patients from the 4 families were enrolled in this study.Two ENG and 1 ACVRL1 mutations were identified,among which an ENG mutation (c.207G＞A; p.L69L) and anACVRL1 mutation (c.817C＞T; p.L273L) have been previously reported.In addition,a novel ENG mutation (c.1004A＞T; p.Q335L) has been found in 3 different families.Similar mutations were not detected in 200 healthy individuals.No mutations of ENG,ACVRL1 and SMAD4 were found in the fourth family.Conclusion A novel mutation c.1004A＞T (p.Q335L) of ENG has been identified in patients with HHT.And there is significant phenotypic variability and genetic heterogeneity with the disease.