title: High frequency of exon 15 deletion in the FANCA gene in Tunisian patients affected with Fanconi anemia disease: implication for diagnosis.
abstract: Tunisian population is characterized by its heterogeneous ethnic background and high rate of consanguinity. In consequence, there is an increase in the frequency of recessive genetic disorders including Fanconi anemia (FA). The aim of this study was to confirm the existence of a founder haplotype among FA Tunisian patients and to identify the associated mutation in order to develop a simple tool for FA diagnosis. Seventy-four unrelated families with a total of 95 FA patients were investigated. All available family members were genotyped with four microsatellite markers flanking FANCA gene. Haplotype analysis and homozygosity mapping assigned 83 patients belonging to 62 families to the FA-A group. A common haplotype was shared by 42 patients from 26 families at a homozygous state while five patients from five families were heterozygous. Among them, 85% were from southern Tunisia suggesting a founder effect. Using multiplex ligation-dependent probe amplification (MLPA) technique, we have also demonstrated that this haplotype is associated with a total deletion of exon 15 in FANCA gene. Identification of a founder mutation allowed genetic counseling in relatives of these families, better bone marrow graft donor selection and prenatal diagnosis. This mutation should be investigated in priority for patients originating from North Africa and Middle East.
authors.affiliation: Department of Histology and Cytogenetics, Institut Pasteur de Tunis Tunis, Tunisia ; Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Amouri
authors.affiliation: Department of Histology and Cytogenetics, Institut Pasteur de Tunis Tunis, Tunisia ; Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
authors.forename: Faten
authors.initials: F
authors.lastname: Talmoudi
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
authors.forename: Olfa
authors.initials: O
authors.lastname: Messaoud
authors.affiliation: Department of Tumour Biology, Institut Curie Paris, France.
authors.forename: Catherine D
authors.initials: CD
authors.lastname: d'Enghien
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
authors.forename: Mariem B
authors.initials: MB
authors.lastname: Rekaya
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
authors.forename: Ines
authors.initials: I
authors.lastname: Allegui
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
authors.forename: Héla
authors.initials: H
authors.lastname: Azaiez
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
authors.forename: Rym
authors.initials: R
authors.lastname: Kefi
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Abdelhak
authors.affiliation: Haematology Department, Hedi Chaker Hospital, University of Sfax Sfax, Tunisia.
authors.forename: Sondes H
authors.initials: SH
authors.lastname: Meseddi
authors.affiliation: Department of Haematology and Transplantation, National Bone Marrow Transplantation Centre Tunis, Tunisia.
authors.forename: Lamia
authors.initials: L
authors.lastname: Torjemane
authors.affiliation: Department of Peadiatric Immuno-Haematology, National Bone Marrow Transplantation Tunis, Tunisia.
authors.forename: Monia
authors.initials: M
authors.lastname: Ouederni
authors.affiliation: Department of Peadiatric Immuno-Haematology, National Bone Marrow Transplantation Tunis, Tunisia.
authors.forename: Fethi
authors.initials: F
authors.lastname: Mellouli
authors.affiliation: Haematology Department, Aziza Othmana Hospital Tunis, Tunisia.
authors.forename: Héla B
authors.initials: HB
authors.lastname: Abid
authors.affiliation: Haematology Department, Aziza Othmana Hospital Tunis, Tunisia.
authors.forename: Lamia
authors.initials: L
authors.lastname: Aissaoui
authors.affiliation: Department of Peadiatric Immuno-Haematology, National Bone Marrow Transplantation Tunis, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bejaoui
authors.affiliation: Department of Haematology and Transplantation, National Bone Marrow Transplantation Centre Tunis, Tunisia.
authors.forename: Tarek B
authors.initials: TB
authors.lastname: Othmen
authors.affiliation: Department of Tumour Biology, Institut Curie Paris, France ; Institut Curie, INSERM U830 Paris, France ; Sorbonne Paris Cité, Université Paris Descartes Paris, France.
authors.forename: Dominique S
authors.initials: DS
authors.lastname: Lyonnet
authors.affiliation: Hôpital Saint-Louis Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Soulier
authors.affiliation: Department of Pediatrics, CHU Hedi Chaker Sfax, Tunisia.
authors.forename: Mongia
authors.initials: M
authors.lastname: Hachicha
authors.affiliation: Laboratory of Transmission, Immunology and Infection Control, Institut Pasteur de Tunis Tunis, Tunisia.
authors.forename: Koussay
authors.initials: K
authors.lastname: Dellagi
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.affiliation: Department of Histology and Cytogenetics, Institut Pasteur de Tunis Tunis, Tunisia.
authors.forename: Tunisian
authors.initials: T
authors.lastname: Fanconi
keywords: Exon 15 deletion; Fanconi anemia; MLPA; founder haplotype; founder mutation