High frequency of exon 15 deletion in the FANCA gene in Tunisian patients affected with Fanconi anemia disease: implication for diagnosis.

Ahlem Amouri (1, 2) , Faten Talmoudi (1, 2) , Olfa Messaoud (2) , Catherine D d'Enghien (3) , Mariem B Rekaya (2) , Ines Allegui (2) , Héla Azaiez (2) , Rym Kefi (2) , Ahlem Abdelhak (2) , Sondes H Meseddi (4) , Lamia Torjemane (5) , Monia Ouederni (6) , Fethi Mellouli (6) , Héla B Abid (7) , Lamia Aissaoui (7) , Mohamed Bejaoui (6) , Tarek B Othmen (5) , Dominique S Lyonnet (3, 8, 9) , Jean Soulier (10) , Mongia Hachicha (11) , Koussay Dellagi (12) , Sonia Abdelhak (2)

1 Département d'Histologie et de Cytogénétique - Institut Pasteur de Tunis
2 LR11IPT05 - Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory
3 Department of tumor biology
4 Hedi Chaker Hospital [Sfax]
5 Department of Haematology and Transplantation
6 Department of Peadiatric Immuno-Haematology
7 Haematology Department
8 U830 - Unité de génétique et biologie des cancers
9 USPC - Université Sorbonne Paris Cité
10 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
11 Department of Pediatrics
12 LR11IPT02 - Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection

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.

Keywords: Exon 15 deletion; Fanconi anemia; founder haplotype; founder mutation; MLPA

Domains: Life Sciences [q-bio]; Human genetics

Ahlem Amouri, Faten Talmoudi, Olfa Messaoud, Catherine D d'Enghien, Mariem B Rekaya, et al.. High frequency of exon 15 deletion in the FANCA gene in Tunisian patients affected with Fanconi anemia disease: implication for diagnosis.. Molecular Genetics and Genomic Medicine, 2014, 2 (2), pp.160-5. ⟨10.1002/mgg3.55⟩. ⟨pasteur-01098539⟩