摘要

背景:家族性腺瘤性息肉病(FAP)是由大肠性腺瘤性息肉病(APC)基因在5q染色体上的种系突变引起的。目的:本研究评估FAP患者肠外病变的基因型-表型相关性。方法:比较来自51个家族的475例FAP患者APC基因突变与7种肠外表现的发生情况。根据不同年龄患者的暴露时间，对其表现频率进行调整。在没有发现APC基因突变的谱系中，分析与染色体5q的连锁和/或评估错配修复基因突变的复制错误特征的肿瘤。结果:来自42个家族(82%)鉴定出APC基因突变的FAP患者肠外表现的表达比未鉴定出突变的患者更频繁(风险比1.2-4.0;皮肤囊肿有显著差异)。皮肤囊肿或肠外癌的存在显著增加了APC基因突变检测的可能性(分别为94%和92%;P < 0.05)。在没有发现APC基因突变的患者中，在一个大家族中发现了与APC基因的连锁(lod = 5.1, theta 0.01)，并且在这9个谱系的16个成员的所有24个肿瘤中不存在复制错误表型。 Expression of pigmented ocular fundus lesions was strongly associated with mutations in codons 541-1309, but no other extraintestinal manifestations were related to mutation position. Multiplicity of extraintestinal manifestations was high with mutation in codons 1465, 1546, and 2621. CONCLUSIONS: Patients with the colorectal phenotype of FAP but no extraintestinal manifestations may have non-truncating mutations of the APC gene or mutation in a gene other than APC or mismatch repair genes. The site of APC gene mutation is associated with pigmented ocular fundus lesions (codons 542-1309) and predisposition to multiplicity of extraintestinal manifestations (codons 1465, 1546, and 2621).