FANCA Gene Mutations in North African Fanconi Anemia Patients

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, cytogene...

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Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p4976
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4976
http://ddd.uab.cat/record/237599
Access Level:acceso abierto
Palabra clave:consanguinity
founder mutations
North Africa
molecular diagnosis
Fanconi anemia
FANCA
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spelling FANCA Gene Mutations in North African Fanconi Anemia PatientsAli, ABMessaoud, OElouej, STalmoudi, FAyed, WMellouli, FOuederni, MHadiji, SDe Sandre-Giovannoli, ADelague, VLevy, NBogliolo, MSurralles, JAbdelhak, SAmouri, Aconsanguinityfounder mutationsNorth Africamolecular diagnosisFanconi anemiaFANCAPopulations 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.FRONTIERS MEDIA SA2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4976http://ddd.uab.cat/record/237599Frontiers in GeneticsISSN: 16648021reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p49762026-06-14T12:41:47Z
dc.title.none.fl_str_mv FANCA Gene Mutations in North African Fanconi Anemia Patients
title FANCA Gene Mutations in North African Fanconi Anemia Patients
spellingShingle FANCA Gene Mutations in North African Fanconi Anemia Patients
Ali, AB
consanguinity
founder mutations
North Africa
molecular diagnosis
Fanconi anemia
FANCA
title_short FANCA Gene Mutations in North African Fanconi Anemia Patients
title_full FANCA Gene Mutations in North African Fanconi Anemia Patients
title_fullStr FANCA Gene Mutations in North African Fanconi Anemia Patients
title_full_unstemmed FANCA Gene Mutations in North African Fanconi Anemia Patients
title_sort FANCA Gene Mutations in North African Fanconi Anemia Patients
dc.creator.none.fl_str_mv 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
author Ali, AB
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv consanguinity
founder mutations
North Africa
molecular diagnosis
Fanconi anemia
FANCA
topic consanguinity
founder mutations
North Africa
molecular diagnosis
Fanconi anemia
FANCA
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4976
http://ddd.uab.cat/record/237599
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4976
http://ddd.uab.cat/record/237599
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv FRONTIERS MEDIA SA
publisher.none.fl_str_mv FRONTIERS MEDIA SA
dc.source.none.fl_str_mv Frontiers in Genetics
ISSN: 16648021
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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