Variable phenotype of familial adenomatous polyposis in pedigrees with 3′ mutation in the APC gene
Variable phenotype of familial adenomatous polyposis in pedigrees with 3′ mutation in the APC gene
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DOI：
10.1136/gut.43.4.548
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发表时间：
1998-10-01
期刊：
影响因子：
24.5
通讯作者：
Giardiello, FM
中科院分区：
文献类型：
--
作者：
Brensinger, JD;Laken, SJ;Giardiello, FM
5号染色体上的腺瘤性结肠息肉病（APC）基因的种系突变导致家族性腺瘤性息肉病。“减毒”表型已被报道在基因的5'端突变（5'至密码子158），但3'端的基因型-表型关系（3'至密码子1596）尚未完全描述。目的-描述和比较APC基因3'端突变家族的结肠直肠和结肠外表型。方法-来自4个APC基因突变位于密码子1979或2644的家族的31名有风险或受影响的成员进行了评估。一些成员在老年有寡息肉病（少于100个结直肠腺瘤）医学，而其他成员在年轻时患有典型的息肉病。在这四个家族中，结直肠癌的平均诊断年龄（50（7）岁）比经典的FAP家系（39（14）岁）要大。FAP的结肠外病变特征发生在3' APC突变，但在家系内和家系间的结肠外表型的变异性和结肠外表现的严重程度与结直肠息肉的数量的分离是noted. Conclusions的APC基因3'突变的家庭表现出可变的家系内表型相似的异质性在近端5'突变的家庭，FAP和寡息肉病家系的基因分型可以指导对受累成员的上、下消化道进行适当的监测。
Background-Germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5 causes familial adenomatous polyposis. "Attenuated" phenotype has been reported with mutation in the 5' end of the gene (5' to codon 158), but genotype-phenotype relations at the 3' end (3' to codon 1596) have not been described fully.Aims-To describe and compare colorectal and extracolonic phenotypes in a case series of families with mutation in the 3' end of the APC gene.Methods-Thirty one at risk or affected members from four families with a mutation in the APC gene located at codon 1979 or 2644 were evaluated.Results-Variable intrapedigree colorectal phenotype was observed: some members at older age had oligopolyposis (fewer University School of than one hundred colorectal adenomas) Medicine whereas other members had classic polyposis at young age. Colorectal cancer was diagnosed at older mean age (50 (7) years) in the four families than in classic FAP pedigrees (39(14) years). Extracolonic lesions characteristic of FAP occurred with 3' APC mutations, but variability in intrapedigree and interpedigree extracolonic phenotype and dissociation of severity of extracolonic manifestations from number of colorectal polyps was noted.Conclusions-Families with 3' mutations of the APC gene exhibit variable intrapedigree phenotype similar to the heterogeneity noted in families with proximal 5' mutations, Genotyping of FAP and oligopolyposis pedigrees can guide appropriate surveillance of the upper and lower gastrointestinal tract in affected members.