Premium
High frequency of exon deletions and putative founder effects in French Canadian Lynch syndrome families
Author(s) -
Chong George,
Jarry Jonathan,
Marcus Victoria,
Thiffault Isabelle,
Winocour Sebastian,
Monczak Yury,
Drouin Régen,
Latreille Jean,
Australie Karlene,
Bapat Bharati,
Gordon Philip H.,
Giguère Yves,
Gologan Adrian,
Galiatsatos Polymnia,
Jass Jeremy R.,
Wong Nora,
Zaor Sonya,
Palma Laura,
Kasprzak Lidia,
Tischkowitz Marc,
Foulkes William D.
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21056
Subject(s) - lynch syndrome , genetics , msh2 , biology , msh6 , mlh1 , pms2 , founder effect , exon , proband , mutation , haplotype , cancer , dna mismatch repair , gene , germline mutation , genotype , colorectal cancer
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. © 2009 Wiley‐Liss, Inc.