title: Mutation screening of the BRCA1 gene in early onset and familial breast/ovarian cancer in Moroccan population.
abstract: Worldwide variation in the distribution of BRCA mutations is well recognised, and for the Moroccan population no comprehensive studies about BRCA mutation spectra or frequencies have been published. We therefore performed mutation analysis of the BRCA1 gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for BRCA testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the BRCA1 gene. 31.6 % (6/19) of familial cases and 1 % (1/102) of early-onset sporadic (< 45 years)were found to be associated with BRCA1 mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA), one missense mutation (c.5095C>T),and one nonsense mutation (c.4942A>T). The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in BRCA1, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55), but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of BRCA2 in BC is also under study.
authors.affiliation: Laboratoire de Recherche et de Biosécurité P3, Hôpital Militaire d'Instruction Mohammed V, Rabat, Maroc.
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Laraqui
authors.forename: Nancy
authors.initials: N
authors.lastname: Uhrhammer
authors.forename: Idriss
authors.initials: I
authors.lastname: Lahlou-Amine
authors.forename: Hicham
authors.initials: H
authors.lastname: El Rhaffouli
authors.forename: Jamila
authors.initials: J
authors.lastname: El Baghdadi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Dehayni
authors.forename: Rahali Driss
authors.initials: RD
authors.lastname: Moussaoui
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ichou
authors.forename: Yassir
authors.initials: Y
authors.lastname: Sbitti
authors.forename: Abderrahman
authors.initials: A
authors.lastname: Al Bouzidi
authors.forename: Said
authors.initials: S
authors.lastname: Amzazi
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
mesh_terms: D000328:Adult; D017668:Age of Onset; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008875:Middle Aged; D009018:Morocco / Q000453:epidemiology; D009154:Mutation; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human
keywords: BRCA1 mutations; Breast cancer; unclassified variants.