medigraphic.com
Órgano Oficial del Instituto Nacional de Pediatría

2023, Número 1

<< Anterior Siguiente >>

Acta Pediatr Mex 2023; 44 (1)


Anemia de Fanconi, Parte 2. Estrategia metodológica para el diagnóstico molecular en pacientes con anemia de Fanconi

Torres L, Juárez U, Reyes P, Frías S

Idioma: Español
Referencias bibliográficas: 52
Paginas: 29-55
Archivo PDF: 505.23 Kb.


RESUMEN

La anemia de Fanconi (AF) es una enfermedad rara, se presenta en 1-5/millón de nacidos vivos. A nivel celular presentan inestabilidad cromosómica, que es la base para su diagnóstico y aunque clínicamente son heterogéneos, hay tres características generales: alteraciones del desarrollo físico, pancitopenia y alto riesgo a desarrollar cáncer. Presenta heterogeneidad genética, hasta ahora se han reportado 22 genes responsables de la AF, 20 de estos genes se heredan de manera autosómica recesiva, uno autosómica dominante y uno ligada al X, sin embargo, existen genes por detectar, ya que a pesar de una minuciosa búsqueda, no en todos los pacientes se logra encontrar la variante patogénica responsable. Debido a esta heterogeneidad, el diagnóstico molecular es complicado, por lo que se necesita una estrategia con varias metodologías como el ensayo de amplificación de sondas dependiente de ligandos múltiples (MLPA), secuenciación de nueva generación, ya sea por panel dirigido (16 genes FANC), o por secuenciación del exoma completo, y microarreglos de alta resolución. Con estas metodologías se pueden detectar grandes deleciones o duplicaciones en los genes FANC, alteraciones puntuales y en el número de copias, así como regiones largas con homocigosidad, con el propósito de encontrar alelos homocigotos. En este artículo presentamos una estrategia detallada para realizar la genotipificación de los pacientes AF mexicanos, con un porcentaje de éxito del 80%.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Fiesco-Roa MÓ, García-de Teresa B, Leal-Anaya P, van ‘t HekR, Wegman-Ostrosky T, Frías S, et al. Fanconi anemia and dyskeratosiscongenita/telomere biology disorders: Two inheritedbone marrow failure syndromes with genomic instability.Front Oncol [Internet]. 2022;12. Available from: https://www.frontiersin.org/articles/10.3389/fonc.2022.949435

  2. García-de-Teresa B, Rodríguez A, Frias S. ChromosomeInstability in Fanconi Anemia: From Breaks to PhenotypicConsequences. Genes (Basel). 2020 Dec;11(12).

  3. Niraj J, Färkkilä A, D’Andrea AD. The Fanconi Anemia Pathwayin Cancer. Annu Rev cancer Biol. 2019 Mar;3:457–78.

  4. Pilonetto D V, Pereira NF, Bonfim CMS, Ribeiro LL, BitencourtMA, Kerkhoven L, et al. A strategy for moleculardiagnostics of Fanconi anemia in Brazilian patients. MolGenet genomic Med. 2017 Jul;5(4):360–72.

  5. Mori M, Hira A, Yoshida K, Muramatsu H, Okuno Y, ShiraishiY, et al. Pathogenic mutations identified by a multimodalityapproach in 117 Japanese Fanconi anemia patients.Haematologica. 2019 Oct;104(10):1962–73.

  6. Ben Haj Ali A, Messaoud O, Elouej S, Talmoudi F, AyedW, Mellouli F, et al. FANCA Gene Mutations in NorthAfrican Fanconi Anemia Patients. Front Genet [Internet].2021;12. Available from: https://www.frontiersin.org/articles/10.3389/fgene.2021.610050

  7. Li LH, Ho SF, Chen CH, Wei CY, Wong WC, Li LY, et al. Longcontiguous stretches of homozygosity in the human genome.Hum Mutat. 2006 Nov;27(11):1115–21.

  8. Pajusalu S, Žilina O, Yakoreva M, Tammur P, Kuuse K, Mölter-Väär T, et al. The Diagnostic Utility of Single Long ContiguousStretches of Homozygosity in Patients without ParentalConsanguinity. Mol Syndromol. 2015 Sep;6(3):135–40.

  9. Wang JC, Ross L, Mahon LW, Owen R, Hemmat M, Wang BT,et al. Regions of homozygosity identified by oligonucleotideSNP arrays: evaluating the incidence and clinical utility. EurJ Hum Genet. 2015 May;23(5):663–71.

  10. Chaves TF, Oliveira LF, Ocampos M, Barbato IT, de Luca GR,Barbato Filho JH, et al. Long contiguous stretches of homozygositydetected by chromosomal microarrays (CMA) inpatients with neurodevelopmental disorders in the Southof Brazil. BMC Med Genomics. 2019 Mar;12(1):50.

  11. Stuppia L, Antonucci I, Palka G, Gatta V. Use of the MLPAassay in the molecular diagnosis of gene copy numberalterations in human genetic diseases. Int J Mol Sci.2012;13(3):3245–76.

  12. Hömig-Hölzel C, Savola S. Multiplex ligation-dependentprobe amplification (MLPA) in tumor diagnostics andprognostics. Diagnostic Mol Pathol Am J Surg Pathol partB. 2012 Dec;21(4):189–206.

  13. Ameziane N, Errami A, Léveillé F, Fontaine C, de Vries Y,van Spaendonk RML, et al. Genetic subtyping of Fanconianemia by comprehensive mutation screening. Hum Mutat.2008 Jan;29(1):159–66.

  14. Castella M, Pujol R, Callén E, Trujillo JP, Casado JA, Gille H,et al. Origin, functional role, and clinical impact of Fanconianemia FANCA mutations. Blood. 2011 Apr;117(14):3759–69.

  15. Kimble DC, Lach FP, Gregg SQ, Donovan FX, Flynn EK, KamatA, et al. A comprehensive approach to identificationof pathogenic FANCA variants in Fanconi anemia patientsand their families. Hum Mutat. 2018 Feb;39(2):237–54.

  16. Kalb R, Neveling K, Hoehn H, Schneider H, Linka Y, BatishSD, et al. Hypomorphic mutations in the gene encoding akey Fanconi anemia protein, FANCD2, sustain a significantgroup of FA-D2 patients with severe phenotype. Am J HumGenet. 2007 May;80(5):895–910.

  17. Flynn EK, Kamat A, Lach FP, Donovan FX, Kimble DC, NarisuN, et al. Comprehensive analysis of pathogenic deletionvariants in Fanconi anemia genes. Hum Mutat. 2014Nov;35(11):1342–53.

  18. Xia B, Dorsman JC, Ameziane N, de Vries Y, RooimansMA, Sheng Q, et al. Fanconi anemia is associated witha defect in the BRCA2 partner PALB2. Nat Genet. 2007Feb;39(2):159–61.

  19. Jung M, Ramanagoudr-Bhojappa R, van Twest S, RostiRO, Murphy V, Tan W, et al. Association of clinical severitywith FANCB variant type in Fanconi anemia. Blood. 2020Apr;135(18):1588–602.

  20. Coffa J, van den Berg J. Analysis of MLPA Data Using NovelSoftware Coffalyser.NET by MRC-Holland. In: Eldin AB,editor. Modern Approaches To Quality Control [Internet].Rijeka: IntechOpen; 2011. Available from: https://doi.org/10.5772/21898

  21. Roy S, Coldren C, Karunamurthy A, Kip NS, Klee EW,Lincoln SE, et al. Standards and Guidelines for ValidatingNext-Generation Sequencing Bioinformatics Pipelines: AJoint Recommendation of the Association for MolecularPathology and the College of American Pathologists. J MolDiagn. 2018 Jan;20(1):4–27.

  22. Hu T, Chitnis N, Monos D, Dinh A. Next-generation sequencingtechnologies: An overview. Hum Immunol. 2021Nov;82(11):801–11.

  23. Voelkerding K V, Coonrod EM, Durtschi JD, Margraf RL.Next-Generation Sequencing: Principles for Clinical ApplicationBT - Molecular Pathology in Clinical Practice.In: Leonard DGB, editor. Cham: Springer InternationalPublishing; 2016. p. 889–909. Available from: https://doi.org/10.1007/978-3-319-19674-9_59

  24. Qin D. Next-generation sequencing and its clinical application.Cancer Biol Med. 2019 Feb;16(1):4–10.

  25. den Dunnen JT. Efficient variant data preparation for HumanMutation manuscripts: Variants and phenotypes.Vol. 40, Human mutation. United States; 2019. p. 1009.

  26. Rizzo JM, Buck MJ. Key principles and clinical applicationsof “next-generation” DNA sequencing. Cancer Prev Res(Phila). 2012 Jul;5(7):887–900.

  27. Sroka I, Frohnmayer L, Wirkkula L. Fanconi Anemia ClinicalCare Guidelines [Internet]. Fifth Edit. Vol. 1, FanconiAnemia Research Fund, Inc. 2020. 1–276 p. Available from:http://marefateadyan.nashriyat.ir/node/150

  28. Bogliolo M, Schuster B, Stoepker C, Derkunt B, Su Y, RaamsA, et al. Mutations in ERCC4, encoding the DNA-repair endonucleaseXPF, cause Fanconi anemia. Am J Hum Genet.2013 May;92(5):800–6.

  29. Hira A, Yoshida K, Sato K, Okuno Y, Shiraishi Y, Chiba K, etal. Mutations in the gene encoding the E2 conjugatingenzyme UBE2T cause Fanconi anemia. Am J Hum Genet.2015 Jun;96(6):1001–7.

  30. Shamseldin HE, Elfaki M, Alkuraya FS. Exome sequencingreveals a novel Fanconi group defined by XRCC2 mutation.J Med Genet. 2012 Mar;49(3):184–6.

  31. Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK,Deignan JL, et al. ACMG clinical laboratory standards fornext-generation sequencing. Genet Med Off J Am Coll MedGenet. 2013 Sep;15(9):733–47.

  32. McCombie WR, McPherson JD, Mardis ER. Next-GenerationSequencing Technologies. Cold Spring Harb Perspect Med.2019 Nov;9(11).

  33. Bao R, Huang L, Andrade J, Tan W, Kibbe WA, Jiang H, et al.Review of current methods, applications, and data managementfor the bioinformatics analysis of whole exomesequencing. Cancer Inform. 2014;13(Suppl 2):67–82.

  34. DePristo MA, Banks E, Poplin R, Garimella K V, MaguireJR, Hartl C, et al. A framework for variation discovery andgenotyping using next-generation DNA sequencing data.Nat Genet. 2011 May;43(5):491–8.

  35. Van der Auwera GA, Carneiro MO, Hartl C, Poplin R,Del Angel G, Levy-Moonshine A, et al. From FastQ datato high confidence variant calls: the Genome AnalysisToolkit best practices pipeline. Curr Protoc Bioinforma.2013;43(1110):11.10.1-11.10.33.

  36. Franke KR, Crowgey EL. Accelerating next generation sequencingdata analysis: an evaluation of optimized bestpractices for Genome Analysis Toolkit algorithms. GenomicsInform. 2020 Mar;18(1):e10.

  37. den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, GreenblattMS, McGowan-Jordan J, et al. HGVS Recommendations forthe Description of Sequence Variants: 2016 Update. HumMutat. 2016 Jun;37(6):564–9.

  38. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J,et al. Standards and guidelines for the interpretation ofsequence variants: a joint consensus recommendation ofthe American College of Medical Genetics and Genomicsand the Association for Molecular Pathology. Genet MedOff J Am Coll Med Genet. 2015 May;17(5):405–24.

  39. Rehder C, Bean LJH, Bick D, Chao E, Chung W, Das S, et al.Next-generation sequencing for constitutional variants inthe clinical laboratory, 2021 revision: a technical standardof the American College of Medical Genetics and Genomics(ACMG). Genet Med Off J Am Coll Med Genet. 2021Aug;23(8):1399–415.

  40. Kumar A, Chordia N. In Silico PCR Primer Designing andValidation BT - PCR Primer Design. In: Basu C, editor. NewYork, NY: Springer New York; 2015. p. 143–51. Availablefrom: https://doi.org/10.1007/978-1-4939-2365-6_10

  41. Callén E, Casado JA, Tischkowitz MD, Bueren JA, CreusA, Marcos R, et al. A common founder mutation inFANCA underlies the world’s highest prevalence of Fanconianemia in Gypsy families from Spain. Blood. 2005Mar;105(5):1946–9.

  42. Whitney MA, Jakobs P, Kaback M, Moses RE, Grompe M.The Ashkenazi Jewish Fanconi anemia mutation: incidenceamong patients and carrier frequency in the at-risk population.Hum Mutat. 1994;3(4):339–41.

  43. García-de Teresa B, Frias S, Molina B, Villarreal MT, RodriguezA, Carnevale A, et al. FANCC Dutch founder mutationin a Mennonite family from Tamaulipas, México. Mol Genetgenomic Med. 2019 Jun;7(6):e710.

  44. Reyes P, García-de Teresa B, Juárez U, Pérez-Villatoro F, Fiesco-Roa MO, Rodríguez A, et al. Fanconi Anemia Patients froman Indigenous Community in Mexico Carry a New FounderPathogenic Variant in FANCG. Int J Mol Sci. 2022 Feb;23(4).

  45. Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F,South ST. American College of Medical Genetics standardsand guidelines for interpretation and reporting of postnatalconstitutional copy number variants. Genet Med Off J AmColl Med Genet. 2011 Jul;13(7):680–5.

  46. Rehm HL, Berg JS, Brooks LD, Bustamante CD, Evans JP,Landrum MJ, et al. ClinGen--the Clinical Genome Resource.N Engl J Med. 2015 Jun;372(23):2235–42.

  47. Matthijs G, Souche E, Alders M, Corveleyn A, Eck S, FeenstraI, et al. Guidelines for diagnostic next-generation sequencing.Eur J Hum Genet. 2016 Oct;24(10):1515.

  48. Smith K, Martindale J, Wallis Y, Bown N, Leo N, Creswell L, etal. General genetic laboratory reporting recommendations.Birmingham Assoc Clin Genet Sci. 2015;11.

  49. Directors ABO. Laboratory and clinical genomic data sharing iscrucial to improving genetic health care: a position statementof the American College of Medical Genetics and Genomics.Genet Med Off J Am Coll Med Genet. 2017 Jul;19(7):721–2.

  50. Federici G, Soddu S. Variants of uncertain significance inthe era of high-throughput genome sequencing: a lessonfrom breast and ovary cancers. J Exp Clin Cancer Res. 2020Mar;39(1):46.

  51. Gregory JJJ, Wagner JE, Verlander PC, Levran O, BatishSD, Eide CR, et al. Somatic mosaicism in Fanconi anemia:evidence of genotypic reversion in lymphohematopoieticstem cells. Proc Natl Acad Sci U S A. 2001Feb;98(5):2532–7.

  52. Ikeda H, Matsushita M, Waisfisz Q, Kinoshita A, OostraAB, Nieuwint AWM, et al. Genetic reversion in an acutemyelogenous leukemia cell line from a Fanconi anemiapatient with biallelic mutations in BRCA2. Cancer Res. 2003May;63(10):2688–94.




2020     |     www.medigraphic.com