medigraphic.com
Órgano Oficial del Instituto Nacional de Pediatría

2022, Number 2

<< Back Next >>

Acta Pediatr Mex 2022; 43 (2)

Fanconi anemia, Part 1. Cytogenetic diagnosis

Molina B, Ramos S, Frias S

Language: Spanish
References: 23
Page: 102-128
PDF size: 572.68 Kb.


ABSTRACT

Fanconi anemia is a rare disease, with a prevalence of 1-5 per million inhabitants; It is caused by the pathogenic variants, usually biallelic, in one of the 22 FANC genes that participate in the FA/BRCA, DNA repair pathway. Accurate diagnosis is crucial for appropriate and timely management and genetic counseling. This can be done through the diepoxybutane or mitomycin C challenge chromosomal aberration test, which is the gold standard for the diagnosis of this disease. This cytogenetic study can be performed in various types of tissues as long as there are cells undergoing mitosis, such as peripheral blood lymphocytes, bone marrow cells, fibroblasts and amniocytes. Both laboratory settings for diagnosis and chromosome analysis can be complex and need to be tightly controlled and interpreted by highly specialized personnel. In this article, we present a step by step guide describing the cytogenetic protocol successfully used in a mexican laboratory, for more than 30 years.


REFERENCES

  1. García-de Teresa B, Rodríguez A, Frias S. Chromosome instability in Fanconi anemia: from breaks to phenotypic consequences. Genes. 2020;21(12):1528. doi: 10.3390/ genes11121528.

  2. Auerbach AD. Diagnosis of Fanconi anemia by diepoxibutane analysis. Curr Protoc Hum Genet. 2015;85: 8.7.1–8.7.17. doi: 10.1002/0471142905.hg0807s85.

  3. Fiesco-Roa M, Giri N, McReynolds LJ, Best AF, Alter BP. Genotype-Phenotype Associations in Fanconi Anemia: A Literature Review. Blood Rev. 2019; 37: 100589. doi: 10.1016/j.blre.2019.100589

  4. Alter BP. Fanconi anemia and the development of leukemia. Best Pract Res Clin Haematol. 2014;27(3-4):214-21. doi: 10.1016/j.beha.2014.10.002.

  5. Savage SA, Walsh MF. Myelodysplastic Syndrome, Acute Myeloid Leukemia, and Cancer Surveillance in Fanconi Anemia. Hematol Oncol Clin. North Am. 2018 ;32(4):657- 668. doi: 10.1016/j.hoc.2018.04.002.

  6. Sawyer SL, Tian L, Kahkonen M, Schwartzentruber J, Kircher M, Majewski J. et al. Biallelic mutations in BRCA1 cause a new Fanconi anemia subtype. Cancer Discov. 2015;5(2):135–142. doi: 10.1158/2159-8290.

  7. Ceccaldi R, Sarangi P, D'Andrea AD. The Fanconi anaemia pathway: new players and new functions. Nat Rev Mol Cell Biol. 2016;17(6):337-49. doi: 10.1038/nrm.2016.48.

  8. Mamrak NE, Shimamura A, Howlett NG. Recent discoveries in the molecular pathogenesis of the inherited bone marrow failure syndrome Fanconi anemia Blood Rev. 2017; 31(3): 93–99. doi: 10.1016/j.blre.2016.10.002.

  9. Garaycoechea J. I. and Patel K. J. Why does the bone marrow fail in Fanconi anemia? Blood. 2014;123: 26-34. 10.1182/blood-2013-09-427740

  10. Rodríguez A and D'Andrea A. Fanconi anemia pathway. Curr Biol. 2017;25;27(18):R986-R988. doi: 10.1016/j. cub.2017.07.043.

  11. Liu W, Palovcak A, Li F, Zafar A, Yuan F, Zhang Y. Fanconi anemia pathway as a prospective target for cancer intervention. Cell Biosci. 2020;16(10):39. doi: 10.1186/s13578- 020-00401-7. eCollection 2020.

  12. Cervenka J, Hirsch BA. Cytogenetic differentiation of Fanconi anemia, "idiopathic" aplastic anemia, and Fanconi anemia heterozygotes. Am J Med Genet. 1983;15(2):211- 23. doi: 10.1002/ajmg.1320150205.

  13. Auerbach AD. Fanconi anemia diagnosis and the diepoxybutane (DEB) test. Exp Hematol. 1993;21(6):731-3.

  14. Nicoletti N, 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. Annals of Hematology 2020; 99:913–924 doi.org/10.1007/s00277-020-03954-2

  15. Fargo JH, Rochowski A, Giri N, Savage SA, Olson SB, Alter BP. 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;144(1):15–27

  16. Lima CSP, Lourenço GJ, Rodriguez DEA, Zocca M, Bertuzzo CS. Cytogenetic and Molecular Diagnosis of Fanconi Anemia. Rev. Bras. Hemoter. 2003;25(3)

  17. doi.org/10.1590/S1516-84842003000300012

  18. Moreno OM, Sánchez AI, Herreño A, Giraldo G, Suárez F, Prieto JC, et al. Phenotypic Characteristics and Copy Number Variants in a Cohort of Colombian Patients with VACTERL Association. Mol Syndromol. 2020;11(5-6):271- 283. doi: 10.1159/000510910

  19. Gutierrez-Gutierrez R, Pupo-Balboa J, Lavaut-Sánchez K, Calixto-Robert Y, Machín-García S. Diagnóstico citogenético de la anemia de Fanconi en pacientes cubanos con sospecha clínica de la enfermedad. Rev Cubana Hematol Inmunol Hemoter. 2021;37(1):e1260.

  20. Auerbach AD. Diagnosis of Fanconi anemia by diepoxibutane analysis. Curr Protoc Hum Genet. 2015;85: 8.7.1–8.7.17. doi: 10.1002/0471142905.hg0807s85.

  21. Castella M, Pujol R, Callén E, Ramírez MJ, Casado JA, Talavera M. et al. Chromosome fragility in patients with Fanconi anaemia: diagnostic implications and clinical impact. J Med Genet. 2011;48(4):242-50. doi: 10.1136/jmg.2010.084210.

  22. Oostra AB, Nieuwint AWM, Joenje H. and de Winter JP. Diagnosis of Fanconi anemia: Chromosomal breakage analysis. Anemia. 2012:238731. doi: 10.1155/2012/238731.

  23. Esmer C, Sánchez S, Ramos S, Molina B, Frias, S. and Carnevale, A. DEB Test for Fanconi Anemia Detection in Patients with Atypical Phenotypes. Am. J. Med. Genet. 2004;124:35–39.




2020     |     www.medigraphic.com