Soravia Claudio, DeLozier Celia D, Dobbie Zurana, Berthod Claudine Rey, Arrigoni Eviano, Bründler Marie-Anne, Blouin Jean-Louis, Foulkes William D, Hutter Pierre
Clinic of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland.
Int J Colorectal Dis. 2005 Sep;20(5):466-470. doi: 10.1007/s00384-005-0764-z.
Heterozygous germline DNA mismatch repair gene mutations are typically associated with HNPCC. Here we report the case of a proband whose father was known for familial adenomatous polyposis. The number of polyps (less than ten) was not typical of polyposis; therefore, the diagnosis of HNPCC was entertained. Microsatellite instability analyses were performed on peripheral blood and biopsy of a right-sided dysplastic adenoma. The tumour tissue showed high-grade instability, and subsequently, immunohistochemistry showed that neither MSH2 nor MSH6 proteins were expressed in tumour cells. Prophylactic colectomy was performed, and an adenocarcinoma developing within the adenoma was diagnosed (pT1N0). Genomic DNA analysis revealed a novel mutation in MSH2 as a frameshift mutation in exon 7 (c.1,191_1,192dupG). Both parents of the proband were analyzed for MSH2 and APC mutations, and in the father, a truncating mutation in exon 15 of APC was identified as del3471-3473GAGA. This mutation was found to be present in the proband. His mother was found to bear the MSH2 exon 7 mutation. At follow-up, the proband was diagnosed with fundic, antral and duodenal adenomas (one fundic adenoma showed low-grade dysplasia). Several tubular rectal adenomas with low-grade dysplasia were excised. The patient later developed an intra-abdominal desmoid tumour.
杂合性种系DNA错配修复基因突变通常与遗传性非息肉病性结直肠癌（HNPCC）相关。在此，我们报告一例先证者的病例，其父亲患有家族性腺瘤性息肉病。息肉数量（少于10个）不符合息肉病的典型特征；因此，考虑诊断为HNPCC。对患者外周血及右侧发育异常腺瘤的活检组织进行了微卫星不稳定性分析。肿瘤组织显示高度不稳定性，随后免疫组化显示肿瘤细胞中MSH2和MSH6蛋白均未表达。患者接受了预防性结肠切除术，术后诊断为腺瘤内发生腺癌（pT1N0）。基因组DNA分析显示MSH2基因外显子7存在一个新的移码突变（c.1,191_1,192dupG）。对先证者的父母进行了MSH2和APC基因突变分析，在其父亲中，APC基因外显子15存在一个截短突变，为del3471 - 3473GAGA。该突变在先证者中也被发现。其母亲被发现携带MSH2基因外显子7突变。随访时，先证者被诊断患有胃底、胃窦和十二指肠腺瘤（一个胃底腺瘤显示低级别发育异常）。切除了几个伴有低级别发育异常的管状直肠腺瘤。患者后来发生了腹内硬纤维瘤。
