摘要
目的探讨一个中国人遗传性非息肉性结直肠癌（heraditary nonpolyposis colorectal cancer，HNPCC）大家系的临床特点，报告基因突变筛查结果。方法调查一个HNPCC大家系，记录的数据包括患者性别，结直肠癌发生的部位，诊断年龄，是否具有同时和（或）异时结直肠癌及结肠外癌，肿瘤的组织病理特点等。抽取家族成员外周血，采用聚合酶链反应和扩增产物直接测序进行基因检测。结果该家系符合阿姆斯特丹Ⅰ标准，4代31人中17例患者共诊断21例次恶性肿瘤。12例（70．6％）患者患有直肠癌，且发病年龄早（平均42．9岁），右半结肠癌多见。基因检测发现一种国内外尚未见报道的MSH2基因的新突变。该突变位于MSH2基因的第7外显子中，由于4个核苷酸（CCGA）的重复导致移码突变，形成截短蛋白。结论HNPCC患者是恶性肿瘤（尤其是结直肠癌）的高发人群。新的MSH2基因突变（MSH2：C．1215-1218dupCCGA）导致该家系遗传性非息肉性结直肠癌的发生。
Objective Hereditary nonpolyposis colorectal cancer （HNPCC） is one of the most common hereditary colon cancer syndromes accounting for 1%-5 % of all colorectal cancer cases. Germline mutations in at least five genes coding for DNA mismatch repair （MMR） proteins are associated with the clinical phenotype of HNPCC. More than 400 MMR mutations have been identified in HNPCC patients, and about 40% of mutations affect MSH2 gene including o nucleotide substitutions, deletions, and insertions. Only a few mutations have been reported in Chinese famihesss. Methods A Chinese family with HNPCC was collected and peripheral blood of individuals from the family was obtained. Mutation analysis was performed on genomic DNA. Results The family fulfilled Amsterdam criteria Ⅰ , and 17 people out of 31 were diagnosed as malignant tumor for 21 times. Twelve people （70.6%） had rectal cancer, and the onset age was young with an average of 42.9 years old. Right side colon cancer was common in the family. A novel duplication mutation of four nucleotides in exon 7 of MSH2 （ MSH2 ：c. 1215 _ 1218dupCCGA） was found, which result in a premature stop 10 codons downstream inMSH2 （p. L407fsX417） in the family. Site-specific PCR was applied to the pre-symptomatic diagnosis. Conclusion This novel genomic mutation of MSH2 was confirmed to be pathogenic, and polymerase chain reaction with modified primer was successfully applied to the pre-symptomatic diagnosis. These data expand the spectntm of MSH2 mutations causing HNPCC.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2007年第2期227-229,共3页
Chinese Journal of Medical Genetics
基金
国家自然科学基金（30270735）
