一个家族性腺瘤性息肉病家系同时出现的APC和MLH1基因突变  

Concurrent APC and MLHI mutations identified in a family affected with familial adenomatous polyposis

作　　者：尚晨光[1] 刘林枝[1] 王小慧[1] 董颖[2] 张岩[1] 

机构地区：[1]北京大学第一医院妇产科,100034 [2]北京大学第一医院病理科,100034

出　　处：《中华医学遗传学杂志》2018年第1期84-88,共5页Chinese Journal of Medical Genetics

摘　　要：目的探讨一个家族性腺瘤性息肉病（familial adenomatous polyposis, FAP）家系APC和MLH1基因的突变情况。方法通过临床表现、家族史及组织病理学等诊断l例FAP女性患者。患者两年后出现子宫内膜上皮内瘤变（endometrial intraepithelial neoplasia, EIN），而后者是Ⅱ型Lynch综合征的病变之一。提取患者及其家系成员的外周血DNA，采用Sanger测序的方法筛查APC和MLH1基因突变。结果该家系同时存在APC基因第7外显子的杂合性突变C．637C〉T（P．R213X）和MLHl基因第12外显子的杂合性突变C．1153C〉T（p．R385C）。两种突变同时出现的情况既往未见报道。前者突变造成终止密码子提前出现，后者突变了造成氨基酸的改变。结论同时出现的APC基因C．637C〉T（P．R213X）和MLHj基因c．1153C〉T（P．R385C）突变是该家系的致病性突变，其出现临床表现的年龄较晚，且严重程度存在差异。对于FAP患者，应询问其家族史并对APC基因进行突变筛查，同时关注其是否存在肠外病变。对于出现子宫内膜病变的患者，可进行MMR基因的筛查，以确定是否同时存在Lynch综合征。Objective To report on concurrent mutations of APC and MII.HI genes identified in a family affected with familial adenomatous polyposis（FAP）. Methods The proband was diagnosed with FAP based on her clinical manifestation, family history and histopathology examination. She developed endornetrial epithelial neoplasia（EIN） two years later. With peripheral blood samples collected from her and members of her family, genomic DNA was extracted, and mutations of the APC and MLH1 genes were analyzed by Sanger sequencing. Results Two novel heterozygous mutations were identified respectively in the APC gene（c. 637C〉T, p. R213X） and the MLH1 gene（c. 1153C〉T, p. R385C） in the proband. The former has resulted in a truncated protein, while the latter has led to substitution of Arginine by Cystine. Conclusion The concurrent mutations of the APC and MLH1 genes probably underline the FAP and Lynch syndrome（I.S） in this pedigree. As the first female identified with such mutations, the proband manifested later onset of symptoms with certain degree of variation. For patient with FAP, a detailed family history should be taken. Potential mutation of the APC gene should be screened. Non intestinal manifestations should be searched. For those who have developed endometrial lesion such as EIN, mutation of the MMR gene （associated with I.S） should also be screened.

关 键 词：家族性腺瘤性息肉病 LYNCH综合征 APC基因 DNA错配修复基因 MLH1基因 

分 类 号：R735.34[医药卫生—肿瘤]