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Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16
- Source :
- American journal of human genetics, 58(2), 300-307. Cell Press, Scopus-Elsevier, American Journal of Human Genetics, 58(2), 300-307. CELL PRESS
- Publication Year :
- 1996
-
Abstract
- Hereditary nonpolyposis colorectal cancer (HNPCC) is a common autosomal dominant cancer susceptibility condition. Inherited mutations in at least four DNA mismatch repair genes, hMSH2, hMLH1, hPMS1, and hPMS2, are known to cause HNPCC. In this study we used denaturing gradient gel electrophoresis (DGGE) to screen for hMLH1 mutations in 34 unrelated HNPCC families (30 Dutch, 3 Italian, and 1 Danish). Ten novel pathogenic germ-line mutations (seven affecting splice sites, two frameshifts, and one in-frame deletion of a single amino acid) have been identified in 12 (35%) of these families. In a previous study, hMSH2 mutations were found in 21% of the same families. While the spectrum of mutations at the hMSH2 gene among HNPCC patients appears heterogeneous, a cluster of hMLH1 mutations has been found in the region encompassing exons 15 and 16, which accounts for 50% of all the independent hMLH1 mutations described to date and for > 20% of the unrelated HNPCC kindreds here analyzed. This unexpected finding has a great practical value in the clinical scenario of genetic services.
- Subjects :
- Male
congenital, hereditary, and neonatal diseases and abnormalities
DNA Repair
Molecular Sequence Data
Polymerase Chain Reaction
GRADIENT GEL-ELECTROPHORESIS
Proto-Oncogene Proteins
Humans
GENETIC INSTABILITY
neoplasms
Germ-Line Mutation
Adaptor Proteins, Signal Transducing
DNA Primers
Genes, Dominant
SPECTRUM
Base Sequence
COLON-CANCER
Nuclear Proteins
nutritional and metabolic diseases
Exons
SINGLE-BASE CHANGES
Colorectal Neoplasms, Hereditary Nonpolyposis
digestive system diseases
Neoplasm Proteins
Pedigree
DNA-Binding Proteins
Europe
POLYPOSIS
HOMOLOG
MutS Homolog 2 Protein
Mutation
Electrophoresis, Polyacrylamide Gel
Female
Carrier Proteins
MutL Protein Homolog 1
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 00029297
- Database :
- OpenAIRE
- Journal :
- American journal of human genetics, 58(2), 300-307. Cell Press, Scopus-Elsevier, American Journal of Human Genetics, 58(2), 300-307. CELL PRESS
- Accession number :
- edsair.pmid.dedup....9e08c6834236dfb0b0395a4a061202c9