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Recurrent and founder mutations in the PMS2 gene
- Publication Year :
- 2012
-
Abstract
- Germline mutations in PMS2 are associated with Lynch syndrome (LS), the most common known cause of hereditary colorectal cancer. Mutation detection in PMS2 has been difficult due to the presence of several pseudogenes, but a custom-designed long-range PCR strategy now allows adequate mutation detection. Many mutations are unique. However some mutations are observed repeatedly, across individuals not known to be related, due to the mutation being either recurrent, arising multiple times de novo at hot spots for mutations, or of founder origin, having occurred once in an ancestor. Previously, we observed 36 distinct mutations in a sample of 61 independently ascertained Caucasian probands of mixed European background with PMS2 mutations. Eleven of these mutations were detected in more than one individual not known to be related and of these, six were detected more than twice. These six mutations accounted for 31 (51%) ostensibly unrelated probands. Here we performed genotyping and haplotype analysis in four mutations observed in multiple probands and found two (c.137G>T and exon 10 deletion) to be founder mutations, one (c.903G>T) a probable founder, and one (c.1A>G) where founder mutation status could not be evaluated. We discuss possible explanations for the frequent occurrence of founder mutations in PMS2.
- Subjects :
- Adenosine Triphosphatases
congenital, hereditary, and neonatal diseases and abnormalities
Genotype
DNA Mutational Analysis
Exons
Colorectal Neoplasms, Hereditary Nonpolyposis
Polymorphism, Single Nucleotide
Article
Founder Effect
DNA-Binding Proteins
DNA Repair Enzymes
Haplotypes
Mutation
Humans
Gene Deletion
Mismatch Repair Endonuclease PMS2
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.pmid..........973aeed305cd4344658a016db3c65bea