Wei S-C, Yu C-Y, Tsai-Wu J-J, Su Y-N, Sheu J-C, Wu C-H H, Wang C-Y, Wong J-M
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
Clin Genet. 2003 Sep;64(3):243-51. doi: 10.1034/j.1399-0004.2003.00123.x.
Hereditary non-polyposis colorectal cancer (HNPCC), the most common type of hereditary colorectal cancer, is thought to be a simple Mendelian disease involving DNA mismatch repair genes. The majority of mutations associated with HNPCC occur in the hMSH2 and hMLH1 genes. The reported incidence of mismatch repair gene mutations in HNPCC kindreds varies considerably (from 22 to 86%), and most mutations are unique. This study aimed to determine the genetic basis of Taiwanese HNPCC kindreds, focusing on the two major genes involved in this disease. A total of 15 Taiwanese HNPCC kindreds meeting the Amsterdam criteria, including 72 affected individuals among a total of 266 individuals, were analyzed using both RNA- and DNA-based methods. The mutation rate of hMSH2 and hMLH1 in these 15 kindreds was 0% and 20%, respectively, which is lower than that reported in other countries. Two novel mutations were discovered in hMLH1: one was an allelic loss of a 5.2-kb genomic fragment causing exon 16 deletion; and the other was a two-nucleotide deletion that resulted in a frameshift mutation of exon 3. We also identified one hMLH1 exon 4 mutation (a C to T transition in codon 117), which had been reported previously in western countries. This is the first genetic study of HNPCC from Taiwan.
遗传性非息肉病性结直肠癌（HNPCC）是最常见的遗传性结直肠癌类型，被认为是一种涉及DNA错配修复基因的简单孟德尔疾病。与HNPCC相关的大多数突变发生在hMSH2和hMLH1基因中。在HNPCC家系中报道的错配修复基因突变发生率差异很大（从22%到86%），而且大多数突变是独特的。本研究旨在确定台湾HNPCC家系的遗传基础，重点关注与该疾病相关的两个主要基因。使用基于RNA和DNA的方法对总共15个符合阿姆斯特丹标准的台湾HNPCC家系进行了分析，这些家系共有266人，其中72人患病。这15个家系中hMSH2和hMLH1的突变率分别为0%和20%，低于其他国家报道的突变率。在hMLH1中发现了两个新突变：一个是5.2 kb基因组片段的等位基因缺失，导致外显子16缺失；另一个是两个核苷酸的缺失，导致外显子3发生移码突变。我们还鉴定出一个hMLH1外显子4突变（密码子117处的C到T转换），这在西方国家之前已有报道。这是台湾首次对HNPCC进行的遗传学研究。
