medigraphic.com
ISSN 1561-2996 (Electronic)
ISSN 0864-0289 (Print)

2021, Number 1

<< Back Next >>

Rev Cubana Hematol Inmunol Hemoter 2021; 37 (1)

Cytogenetic diagnosis of Fanconi anemia in Cuban patients with clinical suspicion of the disease

Gutiérrez GR, Pupo BJ, Lavaut SK, Calixto RY, Machín GS

Language: Spanish
References: 23
Page: 1-16
PDF size: 329.53 Kb.


ABSTRACT

Introduction: Fanconi anemia is a rare genetic disease of autosomal inheritance or X-linked, characterized by genomic instability and hypersensitivity to DNA cross-linking agents like diepoxybutane and mitomycin C (MMC). The basis for its diagnosis is an abnormal response to these substances, which constitutes a unique cell marker and manifests as an increased chromosomal breakage rate.
Objective: To perform the analysis of the chromosomal breakages induced by mitomycin C in peripheral blood lymphocytes of Cuban patients with suspicion of Fanconi anemia.
Methods: A study was conducted of chromosomal breakages induced by mitomycin C at various concentrations in cultures of T lymphocytes from venous peripheral blood of 32 patients with clinical suspicion of Fanconi anemia and an equal number of control subjects.
Results: At the end of the analysis, six patients (20%) were diagnosed with Fanconi anemia. Of these, four showed a high percentage of breakages and two had somatic mosaicism. From a clinical point of view, four had aplastic anemia and two only presented dysmorphic features typical of the disease.
Conclusions: Evaluation of the chromosomal breakages induced by mitomycin C led to the definitive diagnosis of Fanconi anemia in patients with a history of aplastic anemia, even in the absence of congenital anomalies. This is the first study of its type in a group of Cuban patients.


REFERENCES

  1. Mehta PA, Tolar J. Fanconi Anemia. 14 Feb 2002 [updated 8 Mar 2018 ]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews(r) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.

  2. Auerbach AD. Fanconi anemia and its diagnosis. Mutat Res. 2009;668:4-10. DOI: https://10.1016/j.mrfmmm.2009.01.013

  3. Auerbach AD. Diagnosis of Fanconi anemia by diepoxybutane analysis. Curr Protoc Hum Genet. Apr 2015; 85: 8.7.1-17. DOI: https://10.1002/0471142905.hg0807s85

  4. Cheung RS, Taniguchi T. Recent insights into the molecular basis of Fanconi anemia: genes, modifiers, and drivers. Int J Hematol. 2017 Sep;106(3):335-44. DOI: https://10.1007/s12185-017-2283-4

  5. Bagby G. Recent advances in understanding hematopoiesis in Fanconi Anemia. F1000Res. 2018 Jan;7:105. DOI: https://10.12688/f1000research.13213.1

  6. Knies K, Inano Sh, Ramires MJ, Ishiai M, Surrallés J, Takata M et al. Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia. J Clin Invest. Aug 2017;127(8):3013-27. DOI: 10.1172/JCI92069

  7. Online Mendelian Inheritance in Man, OMIM(. Johns Hopkins University, Baltimore, MD. OMIM Number: 609644. FANCM GENE; FANCM. Date last edited: 10/07/2019. Disponible en: Disponible en: https://omim.org/ https://omim.org/entry/609644

  8. Keel SB, Scott A, Sanchez-Bonilla M, PA Ho, Gulsuner S, Pritchard CC, et al. Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients. Haematologica. Nov 2016;101(11):1343-50. DOI: https://10.3324/haematol.2016.149476

  9. Oostra AB, Nieuwint AW, Joenje H, de Winter JP. Diagnosis of fanconi anemia: chromosomal breakage analysis. Anemia. May 2012;2012:238731. DOI: https://10.1155/2012/238731

  10. Giampietro PF, Adler-Brecher B, Verlander PC, Pavlakis SG, Davis JG, Auerbach AD. The need for more accurate and timely diagnosis in Fanconi anemia: a report from the International Fanconi Anemia Registry. Pediatrics. 1993 Jun;91:1116-20.

  11. Taylor AMR, Rothblum-Oviatt C, Ellis NA, Hickson ID, Meyer S, Crawford TO, et al. Chromosome instability syndromes. Nat Rev Dis Primers. 2019 Sep;5(1):64 DOI: https://doi.org/10.1038/s41572-019-0113-0

  12. Gennery AR, Slatter MA, Bhattacharya A, Barge D, Haigh S, O'Driscoll M, et al. The clinical and biological overlap between Nijmegen Breakage Syndrome and Fanconi anemia. Clin Immunol. Nov 2004;113(2):214-9. DOI: https://doi.org/10.1016/j.clim.2004.03.024

  13. Auerbach AD, Rogatko A, Schroeder-Kurth TM. International Fanconi Anemia Registry: relation of clinical symptoms to diepoxybutane sensitivity. Blood. 1989Feb;73:391-6. DOI: https://doi.org/10.1182/blood. V73.2.391.391

  14. Asur RS, Kimble DC, Lach FP, Jung M, Donovan FX, Kamat A, et al. Somatic mosaicism of an intragenic FANCB duplication in both fibroblast and peripheral blood cells observed in a Fanconi anemia patient leads to milder phenotype. Mol Genet Genomic Med. 2018 Jan;6(1):77-91.

  15. Fargo JH, Rochowski A, Giri N, Savage SA, Olson SB, Alter B. Comparison of Chromosome Breakage in Non-Mosaic and Mosaic Patients with Fanconi Anemia, Relatives, and Patients with Other Inherited Bone Marrow Failure Syndromes. Cytogenet Genome Res. 2014 Sep; 144(1):15-27. DOI: https://10.1159/000366251

  16. Nicoletti E, Rao G, Bueren JA, Río P, Navarro S, Surrallés J, et al. Mosaicism in Fanconi anemia: concise review and evaluation of published cases with focus on clinical course of blood count normalization. Ann Hematol. 2020 Feb;99(5):913-24. DOI: https://10.1007/s00277-020-03954-2

  17. West AH, Churpek JE. Old and new tools in the clinical diagnosis of inherited bone marrow failure syndromes. Hematology Am Soc Hematol Educ Program. 2017Dec;2017(1):79-87. DOI: https://10.1182/asheducation-2017.1.79

  18. Brzezniakiewicz-Janus K, Rupa-Matysek J, Gil L. Acquiered aplastic anemia as a clonal disorder of hematopoietic stem cells. Stem cell Rev Rep. 2020Jun;16(3):472-81. DOI: https://10.1007/s12015-020-09971-y

  19. Ishii K, Young NS. Anemia of central origin. Semin Hematol. 2015 Oct;52(4):321-38. DOI: https://10.1053/j.seminhematol.2015.07.002

  20. Ebens ChL, MacMillan ML and Wagner JE. Hematopoietic cell transplantation in Fanconi Anemia: current evidence, challenges and recommendations. Expert Rev Hematol. 2017 Jan;10(1):81-97. DOI: https://10.1080/17474086.2016.1268048

  21. Bogliolo M, Surrallés J. Fanconi anemia: a model disease for studies on human genetics and advanced therapeutics. Curr Opin Genet Dev. 2015 Aug;33:32-40.

  22. Pilonetto DV, Pereira NF, Bonfim CMS, Ribeiro LL, Bitencourt MA, Kerkhoven L, et al. Strategy for molecular diagnostics of Fanconi anemia in Brazilian patients. Mol Genet Genomic Med. 2017 Jul;5(4): 360-72.

  23. Rageul J, Kim H. Fanconi anemia and the underlying causes of genomic instability. Environn Mol Mutagen. 2020 Feb;61(7):693-708. DOI: https://10.1002/em.22358




2020     |     www.medigraphic.com