应用全外显子组测序分析1例腺瘤性息肉病基因缺失突变

Analysis of a case of adenomatous polyposis coli gene deletional mutation by whole-exome sequencing

[目的]分析1例家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)基因的缺失突变,探讨基因突变在FAP发生发展中的作用机制。[方法]抽取先证者及家系成员外周血并提取基因组DNA,应用全外显子组测序(whole-exome sequencing,WES)技术对先证者及家系成员进行检测,并结合内镜检查、病理分析确诊。[结果]家系中发现腺瘤样息肉病(adenomatous polyposis coli,APC)基因杂合缺失c.3927_3931 delAAAGA(p.E1307 Dfs*4),该缺失使APC基因氨基酸编码发生改变,形成一个终止密码子,导致蛋白编码终止,形成截断蛋白。[结论]APC杂合缺失c.3927_3931 delAAAGA导致终止密码子出现是该FAP家系发病的根本原因;WES可以更快、更准确地对患者确诊治疗,为遗传病的早期预防提供新的途径,给遗传咨询和产前诊断提供依据。

[Objective]To analysis a case of familial adenomatous polyposis(FAP)gene deletional mutation and investigate the mechanism of gene mutation in the occurrence and development of FAP.[Methods]The patient and his family members’peripheral blood and genomic DNA were extracted.They were detected by whole-exome sequencing(WES)technique and diagnosed by endoscopy and pathological analysis.[Results]A heterozygous deletion of adenomatous polyposis coli(APC)gene c.39273931 delAAAGA(p.E1309 Dfs*4)was found in the family.This deletion altered the amino acid coding of APC gene and resulted in an early termination codon,which resulting in the stop of protein coding and the formation of truncated proteins.[Conclusions]APC heterozygous deletion c.39273931 delAAAGA leads to the appearance of termination codon,which is the fundamental cause of the FAP family.WES can diagnose and treat patients more quickly and accurately,provide a new way for early prevention of genetic diseases and basis for genetic counseling and prenatal diagnosis.