7个家族性腺瘤样息肉病家系的基因变异分析及遗传咨询  

Genetic analysis and counseling in seven familial adenomatous polyposis families

作　　者：马稔翌 李佑[2] 方旭前[1] MA Renyi;LI You;FANG Xuqian(Department of Pathology,Ruijin Hospital,Shanghai Jiao TongUniversity School of Medicine,Shanghai 200025,China;Department of General Surgery,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院病理科,上海200025 [2]上海交通大学医学院附属瑞金医院普外科,上海200025

出　　处：《胃肠病学和肝病学杂志》2025年第1期1-5,共5页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的分析7个家族样腺瘤样息肉病(familial adenomatous polyposis,FAP)家系的临床病理特点及致病性变异,并据此提供遗传咨询。方法收集患者临床信息,采集先证者病变组织及外周血样本,进行遗传性结直肠癌致病基因筛查;同时,采集家系成员外周血样本进行Sanger测序验证。结果在7例先证者中,5例被发现有Ⅰ类致病性变异,分别为APC p.V677Sfs*3、APC p.E1538*(COSM6041693)、APC p.Q1429*(COSM18836)、APC p.S1281*(COSM19212)、APC p.Q1062*(COSM3696862)。结合家系数据的基因型-表型关联分析,鉴定出APC p.V677Sfs*3为新的APC种系突变。在7例FAP先证者根治术标本中,均存在多发性绒毛状管状腺瘤。通过遗传咨询,1例密集型FAP热点突变携带者(APC p.E1538*)选择预防性手术;2例APC p.V677Sfs*3携带者选择内镜下治疗。结论病理检出多发性绒毛状管状腺瘤高度提示FAP。结合遗传性肠癌致病基因筛查和恰当的干预手段,有助于基因突变携带者降低患癌风险。Objective To evaluate the clinical-pathological features and pathogenic mutations within seven families with familial adenomatous polyposis(FAP),with the goal of providing genetic counseling.Methods Clinical data of probands and their family members were collected.Paraffin-embedded tissues and peripheral blood were collected from probands,and screening for genes associated with hereditary colorectal cancer by next generation sequencing(NGS).Sanger sequencing was utilized to confirm the pathogenicity variation from peripheral blood samples of the family members.Results Among the 7 probands,5 were found to have class I pathogenic variants,including APC p.V677Sfs*3,APC p.E1538*(COSM6041693),APC p.Q1429*(COSM18836),APC p.S1281*(COSM19212)and APC p.Q1062*(COSM3696862).Genotype-phenotype correlation analysis incorporating family data identified APC p.V677Sfs*3 as novel APC germline mutations.Multiple villous and tubular adenomas were detected in the colorectal resection specimens from all seven FAP probands.Guided by genetic counseling,a family member with APC p.E1538*mutation chosed prophylactic surgery,while 2 pathogenic gene carriers with APC p.V677Sfs*3 chosed endoscopic management.Conclusion The presence of multiple villous and tubular adenomas is strongly indicative of FAP.Combining genetic screening and appropriate intervention will be benefit for carriers to reduce their risk of colorectal cancer.

关 键 词：家族性腺瘤样息肉病 APC基因 遗传咨询 

分 类 号：R574[医药卫生—消化系统]