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Diagnosis of Fanconi Anemia: Chromosomal Breakage Analysis

Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessi...

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Autores principales: Oostra, Anneke B., Nieuwint, Aggie W. M., Joenje, Hans, de Winter, Johan P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368163/
https://www.ncbi.nlm.nih.gov/pubmed/22693659
http://dx.doi.org/10.1155/2012/238731
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author Oostra, Anneke B.
Nieuwint, Aggie W. M.
Joenje, Hans
de Winter, Johan P.
author_facet Oostra, Anneke B.
Nieuwint, Aggie W. M.
Joenje, Hans
de Winter, Johan P.
author_sort Oostra, Anneke B.
collection PubMed
description Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked. Cells derived from FA patients are—by definition—hypersensitive to DNA cross-linking agents, such as mitomycin C, diepoxybutane, or cisplatinum, which becomes manifest as excessive growth inhibition, cell cycle arrest, and chromosomal breakage upon cellular exposure to these drugs. Here we provide a detailed laboratory protocol for the accurate assessment of the FA diagnosis as based on mitomycin C-induced chromosomal breakage analysis in whole-blood cultures. The method also enables a quantitative estimate of the degree of mosaicism in the lymphocyte compartment of the patient.
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spelling pubmed-33681632012-06-12 Diagnosis of Fanconi Anemia: Chromosomal Breakage Analysis Oostra, Anneke B. Nieuwint, Aggie W. M. Joenje, Hans de Winter, Johan P. Anemia Research Article Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked. Cells derived from FA patients are—by definition—hypersensitive to DNA cross-linking agents, such as mitomycin C, diepoxybutane, or cisplatinum, which becomes manifest as excessive growth inhibition, cell cycle arrest, and chromosomal breakage upon cellular exposure to these drugs. Here we provide a detailed laboratory protocol for the accurate assessment of the FA diagnosis as based on mitomycin C-induced chromosomal breakage analysis in whole-blood cultures. The method also enables a quantitative estimate of the degree of mosaicism in the lymphocyte compartment of the patient. Hindawi Publishing Corporation 2012 2012-05-24 /pmc/articles/PMC3368163/ /pubmed/22693659 http://dx.doi.org/10.1155/2012/238731 Text en Copyright © 2012 Anneke B. Oostra et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Oostra, Anneke B.
Nieuwint, Aggie W. M.
Joenje, Hans
de Winter, Johan P.
Diagnosis of Fanconi Anemia: Chromosomal Breakage Analysis
title Diagnosis of Fanconi Anemia: Chromosomal Breakage Analysis
title_full Diagnosis of Fanconi Anemia: Chromosomal Breakage Analysis
title_fullStr Diagnosis of Fanconi Anemia: Chromosomal Breakage Analysis
title_full_unstemmed Diagnosis of Fanconi Anemia: Chromosomal Breakage Analysis
title_short Diagnosis of Fanconi Anemia: Chromosomal Breakage Analysis
title_sort diagnosis of fanconi anemia: chromosomal breakage analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368163/
https://www.ncbi.nlm.nih.gov/pubmed/22693659
http://dx.doi.org/10.1155/2012/238731
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