家族性腺瘤性息肉病家系的APC基因突变分析

Analysis on APC gene mutation in familial adenomatous polyposis pedigrees

目的 腺瘤性息肉病基因APC胚系突变是家族性腺瘤性息肉病(FAP)的主要致病原因,文中旨在研究FAP患者的APC基因胚系突变情况,明确其致病原因。方法 选取2017年1月至2021年12月东部战区总医院院消化科住院治疗的3个FAP家系。提取家系成员外周静脉血基因组DNA,应用二代测序(NGS)技术对先证者进行基因检测,应用Sanger测序对先证者及家系成员分别进行变异位点的验证。结果 3个家系均检测到APC基因外显子的杂合性变异,分别为两种无义突变和一种移码突变,其中家系1为第14外显子c.1945C>T(p.Q649X)杂合变异;家系2为第15外显子c.3129_3130delAC(p.Q1044Kfs*2)杂合变异;家系3为第10外显子c.1363C>T(p.Q455X)杂合变异。结论 3个FAP家系均存在致病性APC基因病理性胚系突变,是发病的根本原因,基因检测可以帮助明确诊断,家系受累成员均应筛查肠镜及时治疗。

Objective APC germline mutation of adenomatous polyposis gene is the main cause of familial adenomatous polyposis(FAP). This paper aims to study the germline mutation of APC gene in patients with FAP and identify its cause. Methods Three families with FAP were included hospitalized in Department of Gastroenterology, General Hospital of Eastern Theater Command from January 2017 to December 2021. Genomic DNA of peripheral blood was extracted from the family members, next-generation sequencing(NGS) was applied to detect proband genetically. Then Sanger sequencing was used to verify the mutation sites in probands and their family members respectively. Results Heterozygosity variation of APC gene exon was detected in all three families, including two nonsense mutations and a frameshift mutation, c.1945C>T(p.Q649X) heterozygous variant in exon 14 in family 1;c.3129_3130delAC(p.Q1044Kfs*2) heterozygous variant in exon 15 in family 2;and c.1363C > T(p.Q455X) heterozygous variant in exon 10 in family 3. Conclusion Pathological germline mutation of APC gene exists in all three families with FAP, which is the root cuase of the disease. Genetic detection can help identity diagnosis. Affected family members should be screened by enteroscopy for timely treatment.