Hypomorphic Mutations in the Central Fanconi Anemia Gene FANCD2 Sustain a Significant Group of FA-D2 Patients with Severe Phenotype. Running title : FA-D2 phenotype and FANCD2 mutations

FANCD2 is an evolutionarily conserved Fanconi anemia (FA) gene that plays a central role in DNA double-strand type damage responses. Using complementation assays and immunoblotting, a consortium of American and European groups assigned 29 FA patients from 23 families and 4 additional unrelated patie...

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Autores: Kalba, Reinhard, Neveling, Kornelia, Hoehn, Holger, Schneider, Hildegard, Linka, Yvonne, Batishb, Sat Dev, Hunt, Curtis, Berwick, Marianne, Callén Moréu, Elsa, Surralles, Jordi|||0000-0002-4041-7519, Casado, José A.|||0000-0003-2479-1508, Bueren, Juan|||0000-0002-3228-7013, Dasí, Ángeles, Soulier, Jean|||0000-0002-8734-5356, Gluckman, Eliane, Zwaan, C. Michel, Van Spaendonk, Rosalina, Pals, Gerard, Winter, Johan P. de, Joenje, Hans, Grompe, Markus, Auerbach, Arleen D., Hanenberg, Helmut, Schindler, Detlev
Formato: artículo
Fecha de publicación:2007
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:67767
Acesso em linha:https://ddd.uab.cat/record/67767
https://dx.doi.org/urn:doi:10.1086/517616
Access Level:acceso abierto
Palavra-chave:PREI 2008
Fanconi anemia
FANCD2
Hypomorphic mutations
Splicing
Residual protein
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spelling Hypomorphic Mutations in the Central Fanconi Anemia Gene FANCD2 Sustain a Significant Group of FA-D2 Patients with Severe Phenotype. Running title : FA-D2 phenotype and FANCD2 mutationsKalba, ReinhardNeveling, KorneliaHoehn, HolgerSchneider, HildegardLinka, YvonneBatishb, Sat DevHunt, CurtisBerwick, MarianneCallén Moréu, ElsaSurralles, Jordi|||0000-0002-4041-7519Casado, José A.|||0000-0003-2479-1508Bueren, Juan|||0000-0002-3228-7013Dasí, ÁngelesSoulier, Jean|||0000-0002-8734-5356Gluckman, ElianeZwaan, C. MichelVan Spaendonk, RosalinaPals, GerardWinter, Johan P. deJoenje, HansGrompe, MarkusAuerbach, Arleen D.Hanenberg, HelmutSchindler, DetlevPREI 2008Fanconi anemiaFANCD2Hypomorphic mutationsSplicingResidual proteinFANCD2 is an evolutionarily conserved Fanconi anemia (FA) gene that plays a central role in DNA double-strand type damage responses. Using complementation assays and immunoblotting, a consortium of American and European groups assigned 29 FA patients from 23 families and 4 additional unrelated patients to complementation group FA-D2. This amounts to 3 to 6% of FA patients registered in various datasets. Malformations are frequent in FA-D2 patients and hematological manifestations appear earlier and progress more rapidly when compared to patients from all other FA groups combined, as represented by the International Fanconi Anemia Registry, IFAR. FANCD2 is flanked by two pseudogenes. Mutation analysis revealed the expected total of 66 mutated alleles, 34 of which result in aberrant splicing patterns. Many mutations are recurrent and have ethnic associations and shared alleles. There were no biallelic null mutations so that residual FANCD2 protein of both isotypes was observed in all patients' cell lines available. These analyses suggest that unlike in a knock-out mouse model, total absence of FANCD2 is not existing in FA-D2 patients due to constraints on viable combinations of FANCD2 mutations. Although hypomorphic mutations are involved, the result generally is a relatively severe form of FA. 22007-01-0120072007-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/67767https://dx.doi.org/urn:doi:10.1086/517616reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.https://rightsstatements.org/vocab/InC/1.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:677672026-06-06T12:50:31Z
dc.title.none.fl_str_mv Hypomorphic Mutations in the Central Fanconi Anemia Gene FANCD2 Sustain a Significant Group of FA-D2 Patients with Severe Phenotype. Running title : FA-D2 phenotype and FANCD2 mutations
title Hypomorphic Mutations in the Central Fanconi Anemia Gene FANCD2 Sustain a Significant Group of FA-D2 Patients with Severe Phenotype. Running title : FA-D2 phenotype and FANCD2 mutations
spellingShingle Hypomorphic Mutations in the Central Fanconi Anemia Gene FANCD2 Sustain a Significant Group of FA-D2 Patients with Severe Phenotype. Running title : FA-D2 phenotype and FANCD2 mutations
Kalba, Reinhard
PREI 2008
Fanconi anemia
FANCD2
Hypomorphic mutations
Splicing
Residual protein
title_short Hypomorphic Mutations in the Central Fanconi Anemia Gene FANCD2 Sustain a Significant Group of FA-D2 Patients with Severe Phenotype. Running title : FA-D2 phenotype and FANCD2 mutations
title_full Hypomorphic Mutations in the Central Fanconi Anemia Gene FANCD2 Sustain a Significant Group of FA-D2 Patients with Severe Phenotype. Running title : FA-D2 phenotype and FANCD2 mutations
title_fullStr Hypomorphic Mutations in the Central Fanconi Anemia Gene FANCD2 Sustain a Significant Group of FA-D2 Patients with Severe Phenotype. Running title : FA-D2 phenotype and FANCD2 mutations
title_full_unstemmed Hypomorphic Mutations in the Central Fanconi Anemia Gene FANCD2 Sustain a Significant Group of FA-D2 Patients with Severe Phenotype. Running title : FA-D2 phenotype and FANCD2 mutations
title_sort Hypomorphic Mutations in the Central Fanconi Anemia Gene FANCD2 Sustain a Significant Group of FA-D2 Patients with Severe Phenotype. Running title : FA-D2 phenotype and FANCD2 mutations
dc.creator.none.fl_str_mv Kalba, Reinhard
Neveling, Kornelia
Hoehn, Holger
Schneider, Hildegard
Linka, Yvonne
Batishb, Sat Dev
Hunt, Curtis
Berwick, Marianne
Callén Moréu, Elsa
Surralles, Jordi|||0000-0002-4041-7519
Casado, José A.|||0000-0003-2479-1508
Bueren, Juan|||0000-0002-3228-7013
Dasí, Ángeles
Soulier, Jean|||0000-0002-8734-5356
Gluckman, Eliane
Zwaan, C. Michel
Van Spaendonk, Rosalina
Pals, Gerard
Winter, Johan P. de
Joenje, Hans
Grompe, Markus
Auerbach, Arleen D.
Hanenberg, Helmut
Schindler, Detlev
author Kalba, Reinhard
author_facet Kalba, Reinhard
Neveling, Kornelia
Hoehn, Holger
Schneider, Hildegard
Linka, Yvonne
Batishb, Sat Dev
Hunt, Curtis
Berwick, Marianne
Callén Moréu, Elsa
Surralles, Jordi|||0000-0002-4041-7519
Casado, José A.|||0000-0003-2479-1508
Bueren, Juan|||0000-0002-3228-7013
Dasí, Ángeles
Soulier, Jean|||0000-0002-8734-5356
Gluckman, Eliane
Zwaan, C. Michel
Van Spaendonk, Rosalina
Pals, Gerard
Winter, Johan P. de
Joenje, Hans
Grompe, Markus
Auerbach, Arleen D.
Hanenberg, Helmut
Schindler, Detlev
author_role author
author2 Neveling, Kornelia
Hoehn, Holger
Schneider, Hildegard
Linka, Yvonne
Batishb, Sat Dev
Hunt, Curtis
Berwick, Marianne
Callén Moréu, Elsa
Surralles, Jordi|||0000-0002-4041-7519
Casado, José A.|||0000-0003-2479-1508
Bueren, Juan|||0000-0002-3228-7013
Dasí, Ángeles
Soulier, Jean|||0000-0002-8734-5356
Gluckman, Eliane
Zwaan, C. Michel
Van Spaendonk, Rosalina
Pals, Gerard
Winter, Johan P. de
Joenje, Hans
Grompe, Markus
Auerbach, Arleen D.
Hanenberg, Helmut
Schindler, Detlev
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PREI 2008
Fanconi anemia
FANCD2
Hypomorphic mutations
Splicing
Residual protein
topic PREI 2008
Fanconi anemia
FANCD2
Hypomorphic mutations
Splicing
Residual protein
description FANCD2 is an evolutionarily conserved Fanconi anemia (FA) gene that plays a central role in DNA double-strand type damage responses. Using complementation assays and immunoblotting, a consortium of American and European groups assigned 29 FA patients from 23 families and 4 additional unrelated patients to complementation group FA-D2. This amounts to 3 to 6% of FA patients registered in various datasets. Malformations are frequent in FA-D2 patients and hematological manifestations appear earlier and progress more rapidly when compared to patients from all other FA groups combined, as represented by the International Fanconi Anemia Registry, IFAR. FANCD2 is flanked by two pseudogenes. Mutation analysis revealed the expected total of 66 mutated alleles, 34 of which result in aberrant splicing patterns. Many mutations are recurrent and have ethnic associations and shared alleles. There were no biallelic null mutations so that residual FANCD2 protein of both isotypes was observed in all patients' cell lines available. These analyses suggest that unlike in a knock-out mouse model, total absence of FANCD2 is not existing in FA-D2 patients due to constraints on viable combinations of FANCD2 mutations. Although hypomorphic mutations are involved, the result generally is a relatively severe form of FA.
publishDate 2007
dc.date.none.fl_str_mv 2
2007-01-01
2007
2007-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/67767
https://dx.doi.org/urn:doi:10.1086/517616
url https://ddd.uab.cat/record/67767
https://dx.doi.org/urn:doi:10.1086/517616
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://rightsstatements.org/vocab/InC/1.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://rightsstatements.org/vocab/InC/1.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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