title: Fanconi anemia in Tunisia: high prevalence of group A and identification of new FANCA mutations.
abstract: Fanconi anemia (FA) is a rare autosomal recessive disease characterized by progressive pancytopenia, congenital malformations, and predisposition to acute myeloid leukemia. Fanconi anemia is genetically heterogeneous, with at least eight distinct complementation groups of FA (A, B, C, D1, D2, E, F, and G) having been defined by somatic cell fusion studies. Six genes (FANCA, FANCC, FANCD2, FANCE, FANCG, and FANCF) have been cloned. Mutations of the seventh Fanconi anemia gene, BRCA2, have been shown to lead to FAD1 and probably FAB groups. In order to characterize the molecular defects underlying FA in Tunisia, 39 families were genotyped with microsatellite markers linked to known FA gene. Haplotype analysis and homozygosity mapping assigned 43 patients belonging to 34 families to the FAA group, whereas one family was probably not linked to the FANCA gene or to any known FA genes. For patients belonging to the FAA group, screening for mutations revealed four novel mutations: two small homozygous deletions 1693delT and 1751-1754del, which occurred in exon 17 and exon 19, respectively, and two transitions, viz., 513G-->A in exon 5 and A-->G at position 166 (IVS24+166A-->G) of intron 24. Two new polymorphisms were also identified in intron 24 (IVS24-5G/A and IVS24-6C/G).
authors.affiliation: Laboratoire d'Immunologie, Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur, 1002 Tunis Belvédère, Tunisia.
authors.forename: Chiraz
authors.initials: C
authors.lastname: Bouchlaka
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.forename: Ahlem
authors.initials: A
authors.lastname: Amouri
authors.forename: Hela
authors.initials: H
authors.lastname: Ben Abid
authors.forename: Sondes
authors.initials: S
authors.lastname: Hadiji
authors.forename: Mounir
authors.initials: M
authors.lastname: Frikha
authors.forename: Tarek
authors.initials: T
authors.lastname: Ben Othman
authors.forename: Fethi
authors.initials: F
authors.lastname: Amri
authors.forename: Hammadi
authors.initials: H
authors.lastname: Ayadi
authors.forename: Mongia
authors.initials: M
authors.lastname: Hachicha
authors.forename: Ahmed
authors.initials: A
authors.lastname: Rebaï
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
authors.forename: Koussay
authors.initials: K
authors.lastname: Dellagi
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D005091:Exons; D005192:Family Health; D005199:Fanconi Anemia / Q000235:genetics*; D052217:Fanconi Anemia Complementation Group A Protein; D005260:Female; D017353:Gene Deletion; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007438:Introns; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D005819:Genetic Markers; D011506:Proteins