一个新的APC基因内含子c.531+6T>G变异导致的家族性腺瘤性息肉病病例报告

A case report of c.531+6T>G heterozygous mutation in familial adenomatous polyposis

家族性腺瘤性息肉病(FAP)是一种常染色体显性遗传病,多于15岁左右出现肠道内息肉,后因腹痛、腹胀、便血等临床症状至医院就诊。FAP的发病机制为腺瘤性结肠息肉病(APC)基因的种系突变导致其功能丧失,无法正常调控细胞增殖,最终发展成为恶性肿瘤。我们通过外周血基因检测,发现1例FAP患者APC基因内含子区的一个新突变——c.531+6T>G杂合变异,且其两位姐姐均存在此突变位点且均已发病。APC基因突变导致下游形成一个早期终止密码子,APC蛋白发生截断改变,表达截断蛋白1,从而削弱了APC对细胞增殖的固有抑制作用,导致APC蛋白功能障碍,最终导致疾病恶化。目前尚未发现有这一突变位点的报道,笔者认为在有APC突变的FAP临床表现的患者中,此位点可以作为今后临床基因检测参考点,不应遗漏并应高度重视。

Familial adenomatous polyposis(FAP)is a autosome dominant hereditary disease.Intestinal polyps occur when people are more than 15 years old,and then they go to the hospital for clinical symptoms such as abdominal pain,abdominal distention,and hematochezia.The pathogenesis of FAP is the germline mutation of the adenomatous polyposis coli(APC)gene,which leads to its loss of function and inability to regulate cell proliferation,ultimately causing the development of malignancy.This article reports on a patient with FAP.Through peripheral blood genetic testing,we found a new mutation,c.531+6T>G heterozygous mutation,in the intron region of the APC gene.Furthermore,both of his two sisters have this mutation site.Mutation of the APC gene mainly leads that an early termination codon downstream forms,which causes the APC protein to undergo truncation changes and expresses truncation protein 1,thereby weakening the inherent inhibitory effect of APC on cell proliferation,resulting in APC protein dysfunction and ultimately leading to disease deterioration.There have been no reports of this mutation,but it can be considered in case of APC mutations as well as FAP in patients with clinical manifestations;and it may be used as a reference for preventive clinical treatment in the future.