Frequent mutation in North African patients with MUTYH-associated polyposis

• Published in: Clinical genetics Vol. 80; no. 4; pp. 389 - 393
• Main Authors: Lefevre, JH, Colas, C, Coulet, F, Baert-Desurmont, S, Mongin, C, Tiret, E, Frebourg, T, Soubrier, F, Parc, Y
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2011; Wiley-Blackwell
• Subjects: Adenoma; adenomatous polyposis; Adenomatous Polyposis Coli - genetics; Africa, Northern - ethnology; APC; Biological and medical sciences; Cancer; Colon; Colorectal cancer; DNA Glycosylases - genetics; DNA topoisomerase IV; Ethnic Groups - genetics; Founder Effect; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; General aspects. Genetic counseling; Genes; Genetic Association Studies; Genetic disorders; Genetic markers; Genetics of eukaryotes. Biological and molecular evolution; Haplotypes; Human; Humans; Medical genetics; Medical sciences; Microsatellite Repeats; Microsatellites; Missense mutation; Molecular and cellular biology; Mutation; MUTYH; MUTYH-associated polyposis; polyposis; Population genetics, reproduction patterns; Risk factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Africa, Northern; North Africa; Human; MUTYH-associated polyposis; Rectal disease; Colorectal cancer; Patient; Malignant tumor; Founder effect; Polyposis; Colonic disease; adenomatous polyposis; APC; Digestive diseases; Intestinal disease; Genetics; Mutation; Cancer; MUTYH
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2010.01528.x

Lefevre JH, Colas C, Coulet F, Baert‐Desurmont S, Mongin C, Tiret E, Frebourg T, Soubrier F, Parc Y. Frequent mutation in North African patients with MUTYH‐associated polyposis. 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.