Hutter P, Couturier A, Scott R J, Alday P, Delozier-Blanchet C, Cachat F, Antonarakis S E, Joris F, Gaudin M, D'Amato L, Buerstedde J M
Division de Pathologie, Institut Central des Hôpitaux Valalsans, Slon, Switzerland.
J Med Genet. 1996 Aug;33(8):636-40. doi: 10.1136/jmg.33.8.636.
Hereditary non-polyposis colorectal cancer (HNPCC) is characterised by a genetic predisposition to develop colorectal cancer at an early age and, to a lesser degree, cancer of the endometrium, ovaries, urinary tract, and organs of the gastrointestinal tract other than the colon. In the majority of families the disease is linked to mutations in one of the two mismatch repair genes, hMSH2 or hMLH1. We have found a novel hMLH1 nonsense mutation in a Swiss family with Lynch syndrome, which has been transmitted through at least nine generations. A different tumour spectrum of neoplasms of the skin, soft palate, breast, duodenum, and pancreas was observed in three branches of this family, where there was a virtual absence of colonic tumours. The hMLH1 mutation could not be detected in members of these branches suggesting that at least a second genetic defect predisposing to cancer is segregating in part of the kindred.
遗传性非息肉病性结直肠癌（HNPCC）的特征是具有在早年患结直肠癌的遗传易感性，在较小程度上还易患子宫内膜癌、卵巢癌、泌尿系统癌以及结肠以外的胃肠道器官癌症。在大多数家族中，该疾病与两个错配修复基因hMSH2或hMLH1之一的突变有关。我们在一个患有林奇综合征的瑞士家族中发现了一种新的hMLH1无义突变，该突变已至少遗传了九代。在这个家族的三个分支中观察到皮肤、软腭、乳腺、十二指肠和胰腺肿瘤的不同肿瘤谱，而几乎没有结肠肿瘤。在这些分支的成员中未检测到hMLH1突变，这表明至少第二种致癌遗传缺陷在该家族的部分成员中分离。
