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目的研究1个家族性腺瘤性息肉病家系的腺瘤样息肉病基因(adenomatouspolyposiscoli,APC)的胚系突变。方法经结肠镜、组织病理学检查和家族史的调查,确定了1例家族性腺瘤性息肉病(familialadenomatouspolyposis,FAP)患者。应用多重连接依赖性探针扩增(multiplexligation-dependentprobeamplification,MLPA)、变性高效液相色谱(denaturinghigh-performanceliquidchromatography,DHPLC)和测序等技术对这一家系的成员进行系统的APC全基因筛查。结果在此家系中发现一个新的APC基因的胚系突变c.1999C>T(Q667X),这一突变造成了APC基因终止密码子的形成,从而形成有功能障碍的截短蛋白。临床上,此突变可引起严重的FAP症状,早发结直肠腺瘤和腺癌。结论Q667X胚系突变是引起该家系临床表型的原因,受累成员可考虑大肠预防性切除手术。
Objective To study the germline mutation of adenomatous polyposis coli (APC) in a familial adenomatous polyposis pedigree. Methods One colon cancer patient with familial adenomatous polyposis (FAP) was confirmed by colonoscopy, histopathological examination and family history. The members of this pedigree were systematically screened for APC using multiplex ligation-dependentprobemplification (MLPA), denaturinghigh-performance liquid chromatography (DHPLC) and sequencing. As a result, a germline mutant of the APC gene c.1999C> T (Q667X) was found in this pedigree. This mutation resulted in the formation of the stop codon of the APC gene and the formation of a dysfunctional truncated protein. Clinically, this mutation can cause severe FAP symptoms, premature colorectal adenoma and adenocarcinoma. Conclusion The mutation of Q667X germline is the cause of the clinical phenotype of this pedigree. The affected members may consider the preventive resection of large intestine.