Pedigree and genetic analysis of a novel mutation carrier patient suffering from hereditary nonpolyposis colorectal cancer

作     者：Miklós Tanyi Judith Olasz Géza Lukács Orsolya Csuka László Tóth Zoltán Szentirmay Zsuzsa Ress Zsolt Barta János L Tanyi László Damjanovich 

作者机构：1~(st)Department of SurgeryUniversity of DebrecenMedical and Health Sciences CenterDebrecenHungary Department of PathogeneticsNational Institute of OncologyBudapestHungary Department of PathologyUniversity of DebrecenMedical and Health Sciences CenterDebrecenHungary Department of Human and Experimental Tumor PathologyNational Institute of OncologyBudapestHungary 3~(rd)Department of MedicineUniversity of DebrecenMedical and Health Sciences CenterDebrecenHungary Department of Obstetrics and GynecologyBaylor College of MedicineHoustonTXUnited States 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2006年第12卷第8期

页      面：1192-1197页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Hereditary nonpolyposis colon cancer Bethesda criteria Mutation hMLH1 hMSH2 

摘      要：AIM： To screen a suspected Hungarian HNPCC family to find specific mutations and to evaluate their effect on the presentation of the disease. METHODS： The family was identified by applying the Amsterdam and Bethesda Criteria. Immunohistochemistry was performed, and DNA samples isolated from tumor tissue were evaluated for microsatellite instability. The identification of possible mutations was carried out by sequencing the hMLH1 and hMSH2 genes. RESULTS： Two different mutations were observed in the index patient and in his family members. The first mutation was located in exon 7, codon 422 of hMSH2, and caused a change from Glu to STOP codon. No other report of such a mutation has been published, as far as we could find in the international databases. The second mutation was found in exon 3 codon 127 of the hMSH2 gene, resulting in Asp→Ser substitution. The second mutation was already published, as a non-pathogenic allelic variation. CONCLUSION： The pedigree analysis suggested that the newly detected nonsense mutation in exon 7 of the hMSH2 gene might be responsible for the development of colon cancers. In family members where the exon 7 mutation is not coupled with this missense mutation, colon cancer appears after the age of 40. The association of these two mutations seems to decrease the age of manifestation of the disease into the early thirties.