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Indian Journal of PediatricsVolume 81, Issue 3, March 2014, Pages 260-265

Prevalence of FA-D2 rare complementation group of Fanconi anemia in Serbia(Article)

  • Dragana, V.,
  • Sandra, P.,
  • Emilija, L.,
  • Miloš, K.,
  • Andreja, L.,
  • Ivana, J.,
  • Dragan, M.,
  • Ankica, J.,
  • Željko, Z.,
  • Marija, G.-Š.,
  • Sanja, Ć.,
  • Gordana, J.
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  • aMedical School, University of Belgrade, Belgrade, Serbia
  • bMother and Child Health Care Institute of Serbia Dr. Vukan Cupic, Belgrade, Serbia
  • cVinca Institute of Nuclear Sciences, University of Belgrade, M. Petrovica Alasa 12-14, 11001 Belgrade, Serbia
  • dHospital of Gynecology and Obstetrics Narodni Front, Belgrade, Serbia
  • eFaculty of Biology, University of Belgrade, Belgrade, Serbia

Abstract

Objective: To investigate genetic subtypes of inherited bone marrow failure syndrome Fanconi anemia (FA) in Sebia. FAD2 subtype was found to be the most frequent genetic subtype among investigated FA patients; specific observations of FAD2 phenotype are pointed out. Methods: Several biological endpoints of FA cells in vitro such as radiation-induced level of lymphocyte micronuclei (radiosensitivity), base line and radiation induced level of the DNA double strand breaks (DSBs), leukocyte apoptosis, and telomere capping function were assessed. Results: The results indicate that all FA-D2 patients display radioresistant in vitro response, which is seen as significantly reduced yield of radiation-induced micronuclei. On the contrary, FA-A patients display radiosensitive in vitro response seen as increased number of radiation-induced micronuclei (MN). A massive elimination of irradiated cells via apoptosis is found in both FA-A and FA-D2 subtypes. In FA-A subtype apoptosis positively relates with the yield of radiation-induced MN, whereas in FA-D2 subtype apoptosis relates with a high percentage of cells carrying dysfunctional telomeres. The present results unequivocally demonstrate that cytokinesisblock micronucleus (CBMN) assay and analyses of telomere capping function can be used to distinguish FA-D2 and FA-A complementation groups. Conclusions: Considering all biological endpoints were analyzed, it can be concluded that all FA patients are radiosensitive, regardless of their complementation group. Thus, using CBMN test and telomere capping function analysis can discriminate FA-A from FA-D2 complementation groups, which could be important for assessment the conditioning regimens prior to bone marrow transplantation. © Dr. K C Chaudhuri Foundation 2013.

Author keywords

ApoptosisDNA double strand breaksFa-D2 complementation groupRadiosensitivityTelomere function

Indexed keywords

EMTREE medical terms:adolescentapoptosisarticlebone marrow depressionbone marrow transplantationchildclinical articlecontrolled studyDNA repairdouble stranded DNA breakFanconi anemiafemalefunction testgenetic complementationhumanin vitro studyionizing radiationleukocytemalemicronucleusmicronucleus testprevalenceradiation doseradiation fieldradiosensitivitySerbiatelomereFanconi anemiageneticsphenotypepreschool childprevalence
MeSH:ApoptosisChildChild, PreschoolDNA Breaks, Double-StrandedFanconi AnemiaFemaleHumansMalePhenotypePrevalenceSerbia

Funding details

Funding sponsor Funding number Acronym
Ministerio de Sanidad, Consumo y Bienestar SocialMISAN
Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja173046MPNTR
Ministarstvo Prosvete, Nauke i Tehnološkog RazvojaMPNTR
  • 1

    Acknowledgments The authors are thankful to Prof. Dr. J. Surralles (Center for Biomedical Network Research on Rare Diseases (CIBERER), Bellaterra, Barcelona, Spain) for FA complementation group analysis. This research was supported by Ministry of Health and Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant No. 173046).

  • ISSN: 00195456
  • CODEN: IJPEA
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1007/s12098-013-1284-4
  • PubMed ID: 24317781
  • Document Type: Article
  • Publisher: Springer India

  Gordana, J.; Vinca Institute of Nuclear Sciences, University of Belgrade, M. Petrovica Alasa 12-14, Serbia;
© Copyright 2014 Elsevier B.V., All rights reserved.

Cited by 3 documents

Fiesco-Roa, M.O. , Giri, N. , McReynolds, L.J.
Genotype-phenotype associations in Fanconi anemia: A literature review
(2019) Blood Reviews
Tričković, J.F. , Mandušić, V. , Joksić, I.
Genotyping Fanconi anemia patients from Serbia reveals three novel FANCD2 variants
(2017) Genetika
Filipović, J. , Joksić, G. , Vujić, D.
First molecular-cytogenetic characterization of Fanconi anemia fragile sites in primary lymphocytes of FA-D2 patients in different stages of the disease
(2016) Molecular Cytogenetics
View details of all 3 citations
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