title: First genetic analysis in Tunisian familial adenomatous polyposis probands.
abstract: Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the development of hundreds to thousands of adenomatous polyps in colon and rectum. The APC gene (adenomatous polyposis coli) is considered as the major mutated gene in FAP. It has been shown that biallelic germline mutations in the base-excision-repair gene MYH can be responsible for a recessive inheritance of adenomatous polyposis (AP). This study is the first Tunisian genetic analysis on AP patients. Multiplex ligation-dependent probe amplification (MLPA) was used to screen the APC gene for large genomic rearrangements. The total APC and MYH exon sequences and exon-intron edges were sequenced in an effort to detect germline mutations, four were explored. Mutations were detected in four patients that fulfil the clinical criteria of AP. Three mutations were found in the APC gene, of which two were novel (c.1636_1639delAGTG and c.2514 G>T) and all gave rise to a truncated APC protein. The missense G382D mutation, already described in north and south European populations was found in the MYH gene at the homozygous state in the fourth patient with moderate AP. Our preliminary study provides a basis for implementation of genetic counselling for AP.
authors.affiliation: Laboratoire de Génétique, Immunologie et Pathologies Humaines, Faculté des Sciences de Tunis, Tunis 2092, Tunisia. karim.bougatef@fst.rnu.tn
authors.forename: Karim
authors.initials: K
authors.lastname: Bougatef
authors.forename: Raja
authors.initials: R
authors.lastname: Marrakchi
authors.forename: Amel
authors.initials: A
authors.lastname: Moussa
authors.forename: Yannick
authors.initials: Y
authors.lastname: Blondeau-Lahely
authors.forename: Tawfik
authors.initials: T
authors.lastname: Najjar
authors.forename: Florence
authors.initials: F
authors.lastname: Coulet
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Colas
authors.forename: Farhat
authors.initials: F
authors.lastname: Ben Ayed
authors.forename: Amel
authors.initials: A
authors.lastname: Ben Ammar Elgaaied
authors.forename: Florent
authors.initials: F
authors.lastname: Soubrier
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000208:ethnology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005091:Exons; D005260:Female; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014416:Tunisia
chemical_list: D017931:DNA Primers