title: Frequent mutation in North African patients with MUTYH-associated polyposis.
abstract: MUTYH-associated polyposis (MAP) has been characterized as an autosomal recessive disease predisposing to a variable number of colorectal adenomas with a high risk of cancer. Numerous studies have indicated that two missense mutations (Y179C and G396D) account for about 80% of MUTYH allelic variants in Europeans. Ethnic and geographic differences in the mutation spectrum have been observed. The aim of this study was to report mutations in patients from North Africa, determine the incidence of the c.1227_1228dup mutation in our cohort of MUTYH patients and to evaluate the existence of a founder effect. Within a group of 36 families with MAP, 11 were shown to have a homozygous c.1227_1228dup mutation. These families came from Algeria (n = 5), Tunisia (n = 4), Morocco (n = 1) and Portugal (n = 1). Probands belonging to families of North African origin showed a significantly higher frequency of c.1227_1228dup (78.6% vs 4.5%, p < 0.0001). Haplotype analyses were performed using 10 microsatellite markers surrounding the MUTYH gene spanning a region of 4.4 cM. We identified a common haplotype of at least 1.3 cM in all families suggesting a founder effect for this mutation.
authors: Department of Digestive Surgery, Hopital Saint-Antoine AP-HP, University Paris VI (Pierre and Marie Curie), Paris, France.
authors: J H
authors: JH
authors: Lefevre
authors: C
authors: C
authors: Colas
authors: F
authors: F
authors: Coulet
authors: S
authors: S
authors: Baert-Desurmont
authors: C
authors: C
authors: Mongin
authors: E
authors: E
authors: Tiret
authors: T
authors: T
authors: Frebourg
authors: F
authors: F
authors: Soubrier
authors: Y
authors: Y
authors: Parc
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000352:Africa, Northern / Q000208:ethnology; D045647:DNA Glycosylases / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D018703:Founder Effect; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase