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The Indian Journal of Pediatrics

, Volume 81, Issue 3, pp 260–265 | Cite as

Prevalence of FA-D2 Rare Complementation Group of Fanconi Anemia in Serbia

  • Vujić Dragana
  • Petrović Sandra
  • Lazić Emilija
  • Kuzmanović Miloš
  • Leskovac Andreja
  • Joksić Ivana
  • Mićić Dragan
  • Jovanović Ankica
  • Zečević Željko
  • Guć-Šćekić Marija
  • Ćirković Sanja
  • Joksić GordanaEmail author
Original Article

Abstract

Objective

To investigate genetic subtypes of inherited bone marrow failure syndrome Fanconi anemia (FA) in Sebia. FA-D2 subtype was found to be the most frequent genetic subtype among investigated FA patients; specific observations of FA-D2 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 cytokinesis-block 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.

Keywords

FA-D2 complementation group Radiosensitivity DNA double strand breaks Apoptosis Telomere function 

Notes

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).

Contribution

Joksić Gordana will act as guarantor for this paper.

Conflict of Interest

None.

Role of Funding Source

None.

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Copyright information

© Dr. K C Chaudhuri Foundation 2013

Authors and Affiliations

  • Vujić Dragana
    • 1
    • 2
  • Petrović Sandra
    • 3
  • Lazić Emilija
    • 2
  • Kuzmanović Miloš
    • 1
    • 2
  • Leskovac Andreja
    • 3
  • Joksić Ivana
    • 3
    • 4
  • Mićić Dragan
    • 2
  • Jovanović Ankica
    • 2
  • Zečević Željko
    • 2
  • Guć-Šćekić Marija
    • 2
    • 5
  • Ćirković Sanja
    • 2
  • Joksić Gordana
    • 3
    Email author
  1. 1.Medical SchoolUniversity of BelgradeBelgradeSerbia
  2. 2.Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”BelgradeSerbia
  3. 3.Vinca Institute of Nuclear SciencesUniversity of BelgradeBelgradeSerbia
  4. 4.Hospital of Gynecology and Obstetrics “Narodni Front”BelgradeSerbia
  5. 5.Faculty of BiologyUniversity of BelgradeBelgradeSerbia

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