A founder mutation of MYH associated to adenomatous polyposis and colorectal cancer in North Africa. S. Baert-Desurmont^1,2, A. Rouquette^1,2, J. Mauillon¹, E. Bessenay¹, N. Soufir³, I. Ratbi⁴, A. Sefiani⁴, H. Chaabouni⁵, T. Frebourg^1,2. 1) Department of Genetics, University Hospital, Rouen, France; 2) Inserm U614, Faculty of Medicine, Rouen, France; 3) Department of Genetics, Bichat-Claude Bernard Hospital, Paris, France; 4) Laboratory of Genetics, Faculty of Medicine, Rabat, Morocco; 5) Department of Congenital and Hereditary diseases, Charles Nicolle Hospital, Tunis, Tunisia.
   MYH-associated polyposis (MAP) has been initially characterized as an autosomal recessive disease predisposing to variable number of colorectal adenomas with high risk of degenerescence. Numerous studies have indicated that 2 missense mutations (p.Tyr165Cys in exon 7 and p.Gly382Asp in exon 13) account for about 80 % of MYH allelic variants in Caucasians. During the systematic screening of MYH in patients with colorectal adenomas and / or cancer, we detected in 3 unrelated patients a homozygous germline mutation c.1186_1187insGG, p.Glu396fsX42, within exon 13. The first patient was a woman presenting at 36 years a colorectal adenocarcinoma associated with 6 adenomas. The second subject presented, at the age of 42 years, 2 synchronous colorectal adenocarcinomas and about 20 adenomas. The third patient, a man of 49 years of age, had approximately 30 colorectal and 2 duodenal adenomas. All these individuals originated from North Africa. Analysis of intragenic SNPs and 6 microsatellite markers revealed a common 1.65 cM haplotype between D1S451 and D1S322, suggesting a founder effect. Screening for the c.1186_1187insGG MYH mutation in 150 unrelated healthy individuals from Morocco and Tunisia allowed us to estimate the allelic frequency of this MYH mutation to 0.33%. Considering the high level of consanguinity in North Africa, it is likely that MYH biallelic mutations may contribute to the remarkable frequency of colorectal cancer observed in young patients. In particular, the presence of the c.1186_1187insGG founder mutation should be considered in young patients originated from North Africa presenting sporadic colorectal cancer even with a limited number of adenomas.