FANCA Gene Mutations in North African Fanconi Anemia Patients
Ben Haj Ali, Abir (Institut Pasteur de Tunis. Laboratory of Biomedical Genomics and Oncogenetics)
Messaoud, Olfa (Institut Pasteur de Tunis. Laboratory of Biomedical Genomics and Oncogenetics)
Elouej, Sahar (INSERM, MMG, UMR 1251, Aix Marseille University)
Talmoudi, Faten (Institut Pasteur de Tunis. Laboratory of Biomedical Genomics and Oncogenetics)
Ayed, Wiem (Institut Pasteur de Tunis. Laboratory of Biomedical Genomics and Oncogenetics)
Mellouli, Fethi (Department of Peadiatric Immuno-Haematology, National Bone Marrow Transplantation)
Ouederni, Monia (Department of Peadiatric Immuno-Haematology, National Bone Marrow Transplantation)
Hadiji, Sondes (Haematology Department, Hedi Chaker Hospital, University of Sfax)
De Sandre-Giovannoli, Annachiara (INSERM, MMG, UMR 1251, Aix Marseille University)
Delague, Valérie (INSERM, MMG, UMR 1251, Aix Marseille University)
Lévy, Nicolas (INSERM, MMG, UMR 1251, Aix Marseille University)
Bogliolo, Massimo (Institut d'Investigació Biomèdica Sant Pau)
Surrallés i Calonge, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Abdelhak, Sonia (Institut Pasteur de Tunis. Laboratory of Biomedical Genomics and Oncogenetics)
Amouri, Ahlem (Institut Pasteur de Tunis. Laboratory of Biomedical Genomics and Oncogenetics)
Universitat Autònoma de Barcelona

Fecha:	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 + 166G > 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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Consanguinity ; Founder mutations ; North Africa ; Molecular diagnosis ; Fanconi anemia ; FANCA
Publicado en:	Frontiers in genetics, Vol. 12 (february 2021) , ISSN 1664-8021

DOI: 10.3389/fgene.2021.610050
PMID: 33679882

12 p, 2.2 MB

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