title: High frequency of exon deletions and putative founder effects in French Canadian Lynch syndrome families.
abstract: 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.
authors.affiliation: Departments of Medical Genetics and Oncology, Cancer Prevention Centre, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Chong
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jarry
authors.forename: Victoria
authors.initials: V
authors.lastname: Marcus
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thiffault
authors.forename: Sebastian
authors.initials: S
authors.lastname: Winocour
authors.forename: Yury
authors.initials: Y
authors.lastname: Monczak
authors.forename: Régen
authors.initials: R
authors.lastname: Drouin
authors.forename: Jean
authors.initials: J
authors.lastname: Latreille
authors.forename: Karlene
authors.initials: K
authors.lastname: Australie
authors.forename: Bharati
authors.initials: B
authors.lastname: Bapat
authors.forename: Philip H
authors.initials: PH
authors.lastname: Gordon
authors.forename: Yves
authors.initials: Y
authors.lastname: Giguère
authors.forename: Adrian
authors.initials: A
authors.lastname: Gologan
authors.forename: Polymnia
authors.initials: P
authors.lastname: Galiatsatos
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Jass
authors.forename: Nora
authors.initials: N
authors.lastname: Wong
authors.forename: Sonya
authors.initials: S
authors.lastname: Zaor
authors.forename: Laura
authors.initials: L
authors.lastname: Palma
authors.forename: Lidia
authors.initials: L
authors.lastname: Kasprzak
authors.forename: Marc
authors.initials: M
authors.lastname: Tischkowitz
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D017931:DNA Primers; D018076:DNA, Complementary; D005091:Exons; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D011792:Quebec
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary