Holmberg M, Kristo P, Chadwicks R B, Mecklin J P, Järvinen H, de la Chapelle A, Nyström-Lahti M, Peltomäki P
Department of Medical Genetics, Haartmann Institute, University of Helsinki, Finland.
Hum Mutat. 1998;11(6):482. doi: 10.1002/(SICI)1098-1004(1998)11:6<482::AID-HUMU15>3.0.CO;2-E.
Worldwide, the DNA mismatch repair genes MSH2 and MLH1 account for a major share and almost equal proportions of hereditary nonpolyposis colorectal cancer (HNPCC). Furthermore, the predisposing mutation usually varies from kindred to kindred. In this study, we screen 29 verified or putative HNPCC kindreds from Finland for mutations in these two genes and found 8 different mutations, 7 in MLH1 and 1 in MSH2, occurring in 13 families. Four of these mutations were novel. Altogether, we have to date studied 81 kindreds for mutations and 12 different mutations in 52 families have been identified, 10 in MLH1 and 2 in MSH2. These data show that Finnish HNPCC kindreds are characterized by the predominant involvement of MLH1 (49/52, 94% of the families) and a high rate of shared mutations (5/12, 42%) offering unique possibilities for mutation screening for both research and diagnostic purposes.
在全球范围内，DNA错配修复基因MSH2和MLH1在遗传性非息肉病性结直肠癌（HNPCC）中占主要份额且比例几乎相等。此外，致病突变通常在不同家族中有所不同。在本研究中，我们对来自芬兰的29个已证实或疑似HNPCC家族进行了这两个基因的突变筛查，发现了8种不同的突变，其中7种在MLH1基因，1种在MSH2基因，分布于13个家族。这些突变中有4种是新发现的。迄今为止，我们总共研究了81个家族的突变情况，已在52个家族中鉴定出12种不同的突变，其中10种在MLH1基因，2种在MSH2基因。这些数据表明，芬兰HNPCC家族的特征是MLH1基因受累为主（49/52，占家族的94%）以及共享突变率高（5/12，42%），这为研究和诊断目的的突变筛查提供了独特的可能性。
