title: High prevalence of the c.1227_1228dup (p.Glu410GlyfsX43) mutation in Tunisian families affected with MUTYH-associated-polyposis.
abstract: Germline mutations in the base excision repair gene MUTYH have been associated with recessive inheritance of multiple colorectal adenomas. Screening of the MUTYH gene was carried on index cases of 10 unrelated Tunisian families and on available DNA samples from some members. Three germline mutations: c.536A > G (p.Y179C), c.1187 G > A (p.G396D) and c.1227_1228dup (p.Glu410GlyfsX43), were identified in the homozygous or compound heterozygous state in 8 out of 10 families. The c.1227_1228dup (p.Glu410GlyfsX43) mutation was the most frequent, since it was found in biallelic homozygous in 7 probands and 2 members of family F1 and in compound heterozygous associated with the c.536 A > G (p.Y179C) or c.1187 G > A (p.G396D) in family F2. Haplotype analysis revealed that the 8 families are unrelated. Moreover, in sporadic colorectal cancer, the c.1227_1228dup (p.Glu410GlyfsX43) mutation was identified in 13 % of patients compared to the p.G396D and p.Y179C found in 1.2 and 2.12 % respectively. Our data shows the high prevalence of the p.Glu410GlyfsX43 mutation in Tunisian families affected with MUTYH associated polyposis as well as in sporadic colorectal carcinoma.
authors: Department of Cancer Genetics, Laboratory of Biomass Valorisation and Eukaryotic Protein Expression, Center of Biotechnology of Sfax, University of Sfax, BPK 1177, 3018, Sfax, Tunisia.
authors: Rania
authors: R
authors: Abdelmaksoud-Dammak
authors: Imen
authors: I
authors: Miladi-Abdennadher
authors: Ali
authors: A
authors: Amouri
authors: Nabil
authors: N
authors: Tahri
authors: Lobna
authors: L
authors: Ayadi
authors: Abdelmajid
authors: A
authors: Khabir
authors: Foued
authors: F
authors: Frikha
authors: Ali
authors: A
authors: Gargouri
authors: Raja
authors: R
authors: Mokdad-Gargouri
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D005190:Family; D005260:Female; D018095:Germ-Line Mutation; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015995:Prevalence; D014416:Tunisia
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase