Document Detail

High frequency of exon deletions and putative founder effects in French Canadian Lynch syndrome families.
MedLine Citation:
PMID:  19459153     Owner:  NLM     Status:  MEDLINE    
Lynch syndrome is one of the most common autosomal dominantly inherited cancer syndromes. Mutations in MLH1, MSH2, MSH6, and PMS2 account for greater than 98% of reported mutations in Lynch syndrome families. It has been reported that large genomic deletions in MLH1 and MSH2 are a frequent cause of Lynch syndrome in certain populations. Using a multimodal approach, we have identified mutations in MLH1, MSH2, and MSH6 in French Canadian families fulfilling the Amsterdam criteria for Lynch syndrome and who displayed abnormal staining for at least one of the Lynch syndrome proteins. Mutations were identified in 28 of our 29 French Canadian probands (97%). A total of 18 distinct mutations (nine in MLH1, seven in MSH2, two in MSH6) were identified, of which six (33%) were genomic exon deletions. Another four (22%) resulted in exon deletions in cDNA alone. Three (17%) are novel mutations. Five of these 18 mutations were detected in more than one distinct family (four in MLH1, one in MSH2) and haplotype analysis suggests the possibility of founder effects. Fifteen of the 29 (52%) families carried one of these five putative founder mutations. These findings may simplify genetic testing for Lynch syndrome in French Canadians.
George Chong; Jonathan Jarry; Victoria Marcus; Isabelle Thiffault; Sebastian Winocour; Yury Monczak; Régen Drouin; Jean Latreille; Karlene Australie; Bharati Bapat; Philip H Gordon; Yves Giguère; Adrian Gologan; Polymnia Galiatsatos; Jeremy R Jass; Nora Wong; Sonya Zaor; Laura Palma; Lidia Kasprzak; Marc Tischkowitz; William D Foulkes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human mutation     Volume:  30     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-28     Completed Date:  2009-10-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E797-812     Citation Subset:  IM    
Departments of Medical Genetics and Oncology, Cancer Prevention Centre, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
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MeSH Terms
Base Sequence
Blotting, Southern
Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
DNA Primers
DNA, Complementary
Founder Effect*
Reg. No./Substance:
0/DNA Primers; 0/DNA, Complementary

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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