Seven new mutations in hMSH2, an HNPCC Gene, identified by denaturing gradient-gel electrophoresis

Journal Article · Mon May 01 04:00:00 EDT 1995 · American Journal of Human Genetics

OSTI ID:75446

Wijnen, J; Vasen, H; Khan, P M; Klift, H van der; Leeuwen, C van; Broek, M van den; Leeuwen-Cornelisse, I van; Fodde, R; Menko, F H ^[1]; Nagengast, F ^[2]

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1. Univ. Medical Center, Leiden (Netherlands)
2. Free Univ. Hospital, Amsterdam (Netherlands)

Hereditary nonpolyposis colorectal cancer (HNPCC) is a relatively common autosomal dominant cancer-susceptibility condition. The recent isolation of the DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) responsible for HNPCC has allowed the search for germ-line mutations in affected individuals. In this study we used denaturing gradient-gel electrophoresis to screen for mutations in the hMSH2 gene. Analysis of all the 16 exons of HMSH2, in 34 unrelated HNPCC kindreds, has revealed seven novel pathogenic germ-line mutations resulting in stop codons either directly or through frameshifts. Additionally, nucleotide substitutions giving rise to one missense, two silent, and one useful polymorphism have been identified. The proportion of families in which hMSH2 mutations were found is 21%. Although the spectrum of mutations spread at the hMSH2 gene among HNPCC patients appears extremely heterogeneous, we were not able to establish any correlation between the site of the individual mutations and the corresponding tumor spectrum. Our results indicate that, given the genomic size and organization of the hMSH2 gene and the heterogeneity of its mutation spectrum, a rapid and efficient mutation detection procedure is necessary for routine molecular diagnosis and presymptomatic detection of the disease in a clinical setup. 34 refs., 2 figs., 3 tabs.

• OSTI ID: 75446
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 5 Vol. 56; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DIAGNOSIS
DNA REPAIR
DNA SEQUENCING
DOMINANT MUTATIONS
ELECTROPHORESIS
GENE AMPLIFICATION
GENE MUTATIONS
GENES
HEREDITARY DISEASES
HUMAN CHROMOSOMES
NEOPLASMS
NUCLEOTIDES
PATIENTS
UROGENITAL SYSTEM DISEASES