FANCA Gene Mutations in North African Fanconi Anemia Patients
Por:
Ali, AB, Messaoud, O, Elouej, S, Talmoudi, F, Ayed, W, Mellouli, F, Ouederni, M, Hadiji, S, De Sandre-Giovannoli, A, Delague, V, Levy, N, Bogliolo, M, Surralles, J, Abdelhak, S, Amouri, A
Publicada:
19 feb 2021
Resumen:
Populations in North Africa (NA) are characterized by a high rate of consanguinity. Consequently, the proportion of founder mutations might be higher than expected and could be a major cause for the high prevalence of recessive genetic disorders like Fanconi anemia (FA). We report clinical, cytogenetic, and molecular characterization of FANCA in 29 North African FA patients from Tunisia, Libya, and Algeria. Cytogenetic tests revealed high rates of spontaneous chromosome breakages for all patients except two of them. FANCA molecular analysis was performed using three different molecular approaches which allowed us to identify causal mutations as homozygous or compound heterozygous forms. It included a nonsense mutation (c.2749C>T; p.Arg917Ter), one reported missense mutation (c.1304G>A; p.Arg435His), a novel missense variant (c.1258G>A; p.Asp409Glu), and the FANCA most common reported mutation (c.3788_3790delTCT; p.Phe1263del). Furthermore, three founder mutations were identified in 86.7% of the 22 Tunisian patients: (1) a deletion of exon 15, in 36.4% patients (8/22); (2), a deletion of exons 4 and 5 in 23% (5/22) and (3) an intronic mutation c.2222+66G>A, in 27.3% (6/22). Despite the relatively small number of patients studied, our results depict the mutational landscape of FA among NA populations and it should be taken into consideration for appropriate genetic counseling.
Filiaciones:
Ali, AB:
Univ Tunis El Manar, Inst Pasteur Tunis, Dept Histol & Cytogenet, Tunis, Tunisia
Univ Tunis El Manar, Inst Pasteur Tunis, Lab Biomed Genom & Oncogenet, Tunis, Tunisia
Messaoud, O:
Univ Tunis El Manar, Inst Pasteur Tunis, Lab Biomed Genom & Oncogenet, Tunis, Tunisia
Elouej, S:
Univ Tunis El Manar, Inst Pasteur Tunis, Lab Biomed Genom & Oncogenet, Tunis, Tunisia
Aix Marseille Univ, INSERM, MMG, UMR 1251, Marseille, France
Talmoudi, F:
Univ Tunis El Manar, Inst Pasteur Tunis, Dept Histol & Cytogenet, Tunis, Tunisia
Univ Tunis El Manar, Inst Pasteur Tunis, Lab Biomed Genom & Oncogenet, Tunis, Tunisia
Ayed, W:
Univ Tunis El Manar, Inst Pasteur Tunis, Dept Histol & Cytogenet, Tunis, Tunisia
Univ Tunis El Manar, Inst Pasteur Tunis, Lab Biomed Genom & Oncogenet, Tunis, Tunisia
Mellouli, F:
Natl Bone Marrow Transplantat, Dept Peadiat Immunohaematol, Tunis, Tunisia
Ouederni, M:
Natl Bone Marrow Transplantat, Dept Peadiat Immunohaematol, Tunis, Tunisia
Hadiji, S:
Univ Sfax, Hedi Chaker Hosp, Haematol Dept, Sfax, Tunisia
De Sandre-Giovannoli, A:
Aix Marseille Univ, INSERM, MMG, UMR 1251, Marseille, France
Delague, V:
Aix Marseille Univ, INSERM, MMG, UMR 1251, Marseille, France
Levy, N:
Aix Marseille Univ, INSERM, MMG, UMR 1251, Marseille, France
Bogliolo, M:
Univ Autonoma Barcelona, Hosp Santa Creu & Sant Pau, Res Inst IIB Sant Pau, Barcelona, Spain
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red Enfermedades Raras CIBEREP, Madrid, Spain
Surralles, J:
Univ Autonoma Barcelona, Hosp Santa Creu & Sant Pau, Res Inst IIB Sant Pau, Barcelona, Spain
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red Enfermedades Raras CIBEREP, Madrid, Spain
Abdelhak, S:
Univ Tunis El Manar, Inst Pasteur Tunis, Lab Biomed Genom & Oncogenet, Tunis, Tunisia
Amouri, A:
Univ Tunis El Manar, Inst Pasteur Tunis, Dept Histol & Cytogenet, Tunis, Tunisia
Univ Tunis El Manar, Inst Pasteur Tunis, Lab Biomed Genom & Oncogenet, Tunis, Tunisia
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