Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
권호 표지
DOI QR코드

DOI QR Code

A Case Report of Fanconi Anemia Diagnosed by Genetic Testing Followed by Prenatal Diagnosis

  • Lee, Hwa Jeen (Department of Laboratory Medicine, Seoul National University Hospital) ;
  • Park, Seungman (Department of Laboratory Medicine, Seoul National University Hospital) ;
  • Kang, Hyoung Jin (Department of Pediatrics, Seoul National University Children’s Hospital) ;
  • Jun, Jong Kwan (Department of Obstetrics and Gynecology, Seoul National University Hospital) ;
  • Lee, Jung Ae (Department of Laboratory Medicine, Seoul National University Hospital) ;
  • Lee, Dong Soon (Department of Laboratory Medicine, Seoul National University Hospital) ;
  • Park, Sung Sup (Department of Laboratory Medicine, Seoul National University Hospital) ;
  • Seong, Moon-Woo (Department of Laboratory Medicine, Seoul National University Hospital)
  • Published : 2012.09.01
⟨ Previous Next ⟩

Abstract

Fanconi anemia (FA) is a rare genetic disorder affecting multiple body systems. Genetic testing, including prenatal testing, is a prerequisite for the diagnosis of many clinical conditions. However, genetic testing is complicated for FA because there are often many genes that are associated with its development, and large deletions, duplications, or sequence variations are frequently found in some of these genes. This study describes successful genetic testing for molecular diagnosis, and subsequent prenatal diagnosis, of FA in a patient and his family in Korea. We analyzed all exons and flanking regions of the FANCA, FANCC, and FANCG genes for mutation identification and subsequent prenatal diagnosis. Multiplex ligation-dependent probe amplification analysis was performed to detect large deletions or duplications in the FANCA gene. Molecular analysis revealed two mutations in the FANCA gene: a frameshift mutation c.2546delC and a novel splice-site mutation c.3627-1G>A. The FANCA mutations were separately inherited from each parent, c.2546delC was derived from the father, whereas c.3627-1G>A originated from the mother. The amniotic fluid cells were c.3627-1G>A heterozygotes, suggesting that the fetus was unaffected. This is the first report of genetic testing that was successfully applied to molecular diagnosis of a patient and subsequent prenatal diagnosis of FA in a family in Korea.

Keywords

References

  1. Alter BP. Diagnosis, genetics, and management of inherited bone marrow failure syndromes. Hematology Am Soc Hematol Educ Program 2007;29-39.
  2. Taniguchi T and D'Andrea AD. Molecular pathogenesis of Fanconi anemia: recent progress. Blood 2006;107:4223-33. https://doi.org/10.1182/blood-2005-10-4240
  3. Kutler DI, Singh B, Satagopan J, Batish SD, Berwick M, Giampietro PF, et al. A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood 2003;101:1249-56. https://doi.org/10.1182/blood-2002-07-2170
  4. Rosenberg PS, Greene MH, Alter BP. Cancer incidence in persons with Fanconi anemia. Blood 2003;101:822-6. https://doi.org/10.1182/blood-2002-05-1498
  5. Vaz F, Hanenberg H, Schuster B, Barker K, Wiek C, Erven V, et al. Mutation of the RAD51C gene in a Fanconi anemia-like disorder. Nat Genet 2010;42:406-9. https://doi.org/10.1038/ng.570
  6. Stoepker C, Hain K, Schuster B, Hilhorst-Hofstee Y, Rooimans MA, Steltenpool J, et al. SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype. Nat Genet 2011;43:138-41. https://doi.org/10.1038/ng.751
  7. Wijker M, Morgan NV, Herterich S, van Berkel CG, Tipping AJ, Gross HJ, et al. Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene. Eur J Hum Genet 1999;7:52-9. https://doi.org/10.1038/sj.ejhg.5200248
  8. Bouchlaka C, Abdelhak S, Amouri A, Ben Abid H, Hadiji S, Frikha M, et al. Fanconi anemia in Tunisia: high prevalence of group A and identification of new FANCA mutations. J Hum Genet 2003;48:352-61. https://doi.org/10.1007/s10038-003-0037-z
  9. Callen E, Tischkowitz MD, Creus A, Marcos R, Bueren JA, Casado JA, et al. Quantitative PCR analysis reveals a high incidence of large intragenic deletions in the FANCA gene in Spanish Fanconi anemia patients. Cytogenet Genome Res 2004;104:341-5. https://doi.org/10.1159/000077513
  10. Soulier J, Leblanc T, Larghero J, Dastot H, Shimamura A, Guardiola P, et al. Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway. Blood 2005;105:1329-36.
  11. Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G. Relative quantification of 40 nucleic acid sequences by multiplex ligation- dependent probe amplification. Nucleic Acids Res 2002;30:e57. https://doi.org/10.1093/nar/gnf056
  12. Kook H, Cho D, Cho SH, Hong WP, Kim CJ, Park JY, et al. Fanconi anemia screening by diepoxybutane and mitomicin C tests in Korean children with bone marrow failure syndromes. J Korean Med Sci 1998;13:623-8. https://doi.org/10.3346/jkms.1998.13.6.623
  13. Yamashita T and Nakahata T. Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes. Int J Hematol 2001;74:33-41. https://doi.org/10.1007/BF02982547
  14. Grompe M and D'Andrea A. Fanconi anemia and DNA repair. Hum Mol Genet 2001;10:2253-9. https://doi.org/10.1093/hmg/10.20.2253
  15. Tischkowitz MD and Hodgson SV. Fanconi anaemia. J Med Genet 2003;40:1-10. https://doi.org/10.1136/jmg.40.1.1
  16. Pinto FO, Leblanc T, Chamousset D, Le Roux G, Brethon B, Cassinat B, et al. Diagnosis of Fanconi anemia in patients with bone marrow failure. Haematologica 2009;94:487-95. https://doi.org/10.3324/haematol.13592
  17. Bechtold A, Friedl R, Kalb R, Gottwald B, Neveling K, Gavvovidis I, et al. Prenatal exclusion/confirmation of Fanconi anemia via flow cytometry: a pilot study. Fetal Diagn Ther 2006;21:118-24. https://doi.org/10.1159/000089061

Cited by

  1. Current insights into inherited bone marrow failure syndromes vol.57, pp.8, 2012, https://doi.org/10.3345/kjp.2014.57.8.337
  2. Prenatal diagnosis of single gene disorders using amniotic fluid as the starting material for PCR vol.141, pp.1, 2012, https://doi.org/10.1039/c5an01840d
  3. Screening for mutations in two exons of FANCG gene in Pakistani population vol.161, pp.2, 2012, https://doi.org/10.5507/bp.2017.030