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Genomic sequence analysis of hMSH2 and hMLHL in high and low risk groups

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Original languageEnglish
JournalFASEB Journal
Volume11
Issue number9
Publication statusPublished - 1 Dec 1997

Abstract

Hereditary nonpolyposis colorectal cancer (HNPCC) is an aiHosomal dominant inherited disease characterized by predisposition to colorectal carcinoma (CRC) at an early age. Two (hMSH2. hMLHl I of the lour genes identified and shown to be altered in the germline of HNPCC patients account for the majority of mutations. To establish criteria for clinical laboratory testing, we compared genomic DNA sequence analysis of these two genes in control donors (n=20) and patients (n=59) with early onset CRC (<40 years). Eighteen (30%) different germline mutations were identified in the high-risk group. A splicing mutation was identified in two control donors (10%) and six (30%) were categorized as "indeterminate" as there is no evidence linking the mutations to disease. We also analyzed four HNPCC families for mutations found in their respective proband and identified all eleven (100%) affected family members and three who are at risk. Analysis of individuals at high risk for CRC minimizes ambiguities between mutations and non-disease polymorphisms.

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