Prognostic significance of mutation type and chromosome fragility in Fanconi anemia Article Swipe
Marı́a José Ramı́rez
,
Roser Pujol
,
Jordi Minguillón
,
Massimo Bogliolo
,
Ilaria Persico
,
Debora Cavero
,
Aurora de la Cal
,
Paula Rı́o
,
Susana Navas Navarro
,
José Antonio Casado
,
Almudena Bailador
,
Antonio de la Fuente
,
Miguel López de Heredia
,
F.M. Almazán-Fernández
,
María Luisa Antelo
,
Bienvenida Argilés
,
Isabel Badell
,
Marta Bernués
,
Cristina Beléndez
,
Mar Bermúdez
,
Marta Bernués
,
María Isabel Buedo
,
Estela Carrasco
,
Albert Català
,
Dolors Costa
,
Isabel Cuesta
,
Rafael Fernández‐Delgado
,
Ana Fernández‐Teijeiro
,
Á Figuera
,
Marta Rizo García
,
Ainhoa Gondra
,
Macarena González
,
Soledad González Muñíz
,
Inés Hernández‐Rodríguez
,
Fátima Ibáñez
,
Nicholas Kelleher
,
Francisco Lendínez
,
Mónica López‐Duarte
,
Ricardo López Almaraz
,
Inmaculada Marchante
,
Carmen Mendoza
,
J. M. Nieto
,
Emilio Ojeda
,
Salvador Payán‐Pernía
,
Irene Peláez
,
Inmaculada Pérez de Soto
,
Raquel Portugal
,
María A. Ramos‐Arroyo
,
Alexandra Regueiro
,
Ana Rodríguez
,
Jordi Rosell
,
Raquel Sáez González
,
José Luis Sánchez Sánchez
,
Martha Alejandra Morales‐Sánchez
,
M. Leonor Senent
,
Maria C. Tapia
,
Juan Pablo Trujillo‐Quintero
,
José Manuel Vagace
,
Jaime Verdú‐Amorós
,
Victória Verdugo
,
Isabel Vidales
,
Jose Alfredo Carrizalez Villarreal
,
Cristina Díaz de Heredia
,
Julián Sevilla
,
Juan A. Bueren
,
Jordi Surrallés
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/ajh.27520
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/ajh.27520
Fanconi anemia (FA) is a rare genetic disease characterized by high phenotypic and genotypic heterogeneity, and extreme chromosome fragility. To better understand the natural history of FA, identify genetic risk and prognostic factors, and develop novel therapeutic strategies, the Spanish Registry of Patients with FA collects data on clinical features, chromosome fragility, genetic subtypes, and DNA sequencing with informed consent of participating individuals. In this article, we describe the clinical evolution of 227 patients followed up for up to 30 years, for whom our data indicate a cumulative cancer incidence of 86% by age 50. We found that patients with lower chromosome fragility had a milder malformation spectrum and better outcomes in terms of later‐onset hematologic impairment, less severe bone marrow failure, and lower cancer risk. We also found that outcomes were better for patients with mutations leading to mutant FANCA protein expression (genetic hypomorphism) than for patients lacking this protein. Likewise, prognosis was consistently better for patients with biallelic mutations in FANCD2 (mainly hypomorphic mutations) than for patients with biallelic mutations in FANCA and FANCG , with the lack of the mutant protein in patients with biallelic mutations in FANCG contributing to their poorer outcomes. Our results regarding the clinical impact of chromosome fragility and genetic hypomorphism suggest that mutant FA proteins retain residual activity. This finding should encourage the development of novel therapeutic strategies aimed at partially or fully enhancing mutant FA function, thereby preventing or delaying bone marrow failure and cancer in patients with FA. Clinical Trial Registration number: NCT06490510.
Related Topics
Concepts
FANCA
Fanconi anemia
Bone marrow failure
Biology
Mutation
Genetics
FANCD2
Oncology
Bioinformatics
Medicine
Cancer research
DNA repair
Gene
Stem cell
Haematopoiesis
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/ajh.27520
- OA Status
- green
- Cited By
- 11
- References
- 35
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4404555263
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4404555263Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/ajh.27520Digital Object Identifier
- Title
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Prognostic significance of mutation type and chromosome fragility in Fanconi anemiaWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-11-19Full publication date if available
- Authors
-
Marı́a José Ramı́rez, Roser Pujol, Jordi Minguillón, Massimo Bogliolo, Ilaria Persico, Debora Cavero, Aurora de la Cal, Paula Rı́o, Susana Navas Navarro, José Antonio Casado, Almudena Bailador, Antonio de la Fuente, Miguel López de Heredia, F.M. Almazán-Fernández, María Luisa Antelo, Bienvenida Argilés, Isabel Badell, Marta Bernués, Cristina Beléndez, Mar Bermúdez, Marta Bernués, María Isabel Buedo, Estela Carrasco, Albert Català, Dolors Costa, Isabel Cuesta, Rafael Fernández‐Delgado, Ana Fernández‐Teijeiro, Á Figuera, Marta Rizo García, Ainhoa Gondra, Macarena González, Soledad González Muñíz, Inés Hernández‐Rodríguez, Fátima Ibáñez, Nicholas Kelleher, Francisco Lendínez, Mónica López‐Duarte, Ricardo López Almaraz, Inmaculada Marchante, Carmen Mendoza, J. M. Nieto, Emilio Ojeda, Salvador Payán‐Pernía, Irene Peláez, Inmaculada Pérez de Soto, Raquel Portugal, María A. Ramos‐Arroyo, Alexandra Regueiro, Ana Rodríguez, Jordi Rosell, Raquel Sáez González, José Luis Sánchez Sánchez, Martha Alejandra Morales‐Sánchez, M. Leonor Senent, Maria C. Tapia, Juan Pablo Trujillo‐Quintero, José Manuel Vagace, Jaime Verdú‐Amorós, Victória Verdugo, Isabel Vidales, Jose Alfredo Carrizalez Villarreal, Cristina Díaz de Heredia, Julián Sevilla, Juan A. Bueren, Jordi SurrallésList of authors in order
- Landing page
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https://doi.org/10.1002/ajh.27520Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://digital.csic.es/bitstream/10261/390588/1/Prognostic_significance_mutation_Ramirez.pdfDirect OA link when available
- Concepts
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FANCA, Fanconi anemia, Bone marrow failure, Biology, Mutation, Genetics, FANCD2, Oncology, Bioinformatics, Medicine, Cancer research, DNA repair, Gene, Stem cell, HaematopoiesisTop concepts (fields/topics) attached by OpenAlex
- Cited by
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11Total citation count in OpenAlex
- Citations by year (recent)
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2025: 11Per-year citation counts (last 5 years)
- References (count)
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35Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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