Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Current insights into inherited bone marrow failure syndromes

  • Chung, Nack-Gyun (Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Myungshin (Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • Received : 2014.04.03
  • Accepted : 2014.06.09
  • Published : 2014.08.10
Download PDF
⟨ Previous Next ⟩

Abstract

Inherited bone marrow failure syndrome (IBMFS) encompasses a heterogeneous and complex group of genetic disorders characterized by physical malformations, insufficient blood cell production, and increased risk of malignancies. They often have substantial phenotype overlap, and therefore, genotyping is often a critical means of establishing a diagnosis. Current advances in the field of IBMFSs have identified multiple genes associated with IBMFSs and their pathways: genes involved in ribosome biogenesis, such as those associated with Diamond-Blackfan anemia and Shwachman-Diamond syndrome; genes involved in telomere maintenance, such as dyskeratosis congenita genes; genes encoding neutrophil elastase or neutrophil adhesion and mobility associated with severe congenital neutropenia; and genes involved in DNA recombination repair, such as those associated with Fanconi anemia. Early and adequate genetic diagnosis is required for proper management and follow-up in clinical practice. Recent advances using new molecular technologies, including next generation sequencing (NGS), have helped identify new candidate genes associated with the development of bone marrow failure. Targeted NGS using panels of large numbers of genes is rapidly gaining potential for use as a cost-effective diagnostic tool for the identification of mutations in newly diagnosed patients. In this review, we have described recent insights into IBMFS and how they are advancing our understanding of the disease's pathophysiology; we have also discussed the possible implications they will have in clinical practice for Korean patients.

Keywords

References

  1. Shimamura A, Alter BP. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev 2010;24:101-22.
  2. Kook H. Fanconi anemia: current management. Hematology 2005; 10 Suppl 1:108-10.
  3. Bessler MP, Lin DC, Wilson DB. Inherited bone marrow failure syndromes. In: Orkin SH, Ginsburg D, editors. Nathan and Oski's hematology of infancy and childhood. 7th ed. Philadelphia, PA: WB Saunders, 2008:351-60.
  4. Alter BP. Fanconi's anaemia and its variability. Br J Haematol 1993;85:9-14.
  5. Gregory JJ Jr, Wagner JE, Verlander PC, Levran O, Batish SD, Eide CR, et al. Somatic mosaicism in Fanconi anemia: evidence of genotypic reversion in lymphohematopoietic stem cells. Proc Natl Acad Sci U S A 2001;98:2532-7.
  6. Lee JJ, Yun KB, Kim SY, Lee MJ, Jung HJ, Park JE, et al. A case of Fanconi anemia diagnosed by a chromosome breakage test with skin fibroblasts. Korean J Hematol 2008;43:62-7.
  7. Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014 [cited 2014 May 12]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1401/.
  8. Osorio A, Bogliolo M, Fernandez V, Barroso A, de la Hoya M, Caldes T, et al. Evaluation of rare variants in the new fanconi anemia gene ERCC4 (FANCQ) as familial breast/ovarian cancer susceptibility alleles. Hum Mutat 2013;34:1615-8.
  9. Kee Y, D'Andrea AD. Expanded roles of the Fanconi anemia pathway in preserving genomic stability. Genes Dev 2010;24:1680-94.
  10. Liu T, Ghosal G, Yuan J, Chen J, Huang J. FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair. Science 2010;329:693-6.
  11. Auerbach AD, Greenbaum J, Pujara K, Batish SD, Bitencourt MA, Kokemohr I, et al. Spectrum of sequence variation in the FANCG gene: an International Fanconi Anemia Registry (IFAR) study. Hum Mutat 2003;21:158-68.
  12. Yagasaki H, Oda T, Adachi D, Nakajima T, Nakahata T, Asano S, et al. Two common founder mutations of the fanconi anemia group G gene FANCG/XRCC9 in the Japanese population. Hum Mutat 2003;21:555.
  13. Park J, Chung NG, Chae H, Kim M, Lee S, Kim Y, et al. FANCA and FANCG are the major Fanconi anemia genes in the Korean population. Clin Genet 2013;84:271-5.
  14. Lee HJ, Park S, Kang HJ, Jun JK, Lee JA, Lee DS, et al. A case report of Fanconi anemia diagnosed by genetic testing followed by prenatal diagnosis. Ann Lab Med 2012;32:380-4.
  15. Ameziane N, Sie D, Dentro S, Ariyurek Y, Kerkhoven L, Joenje H, et al. Diagnosis of fanconi anemia: mutation analysis by next-generation sequencing. Anemia 2012;2012:132856.
  16. Knies K, Schuster B, Ameziane N, Rooimans M, Bettecken T, de Winter J, et al. Genotyping of fanconi anemia patients by whole exome sequencing: advantages and challenges. PLoS One 2012;7:e52648.
  17. Rosenberg PS, Greene MH, Alter BP. Cancer incidence in persons with Fanconi anemia. Blood 2003;101:822-6.
  18. Alter BP. Cancer in Fanconi anemia, 1927-2001. Cancer 2003;97:425-40.
  19. Lee DW, Yang JH, Won CH, Chang SE, Lee MW, Choi JH, et al. A case of congenital pigmented dermatofibrosarcoma protuberans (Bednar tumor) in a patient with Fanconi anemia. Pediatr Dermatol 2011;28:583-5.
  20. Woo HI, Kim HJ, Lee SH, Yoo KH, Koo HH, Kim SH. Acute myeloid leukemia with complex hypodiploidy and loss of heterozygosity of 17p in a boy with Fanconi anemia. Ann Clin Lab Sci 2011;41:66-70.
  21. Yoon BG, Kim HN, Han UJ, Jang HI, Han DK, Baek HJ, et al. Long-term follow-up of Fanconi anemia: clinical manifestation and treatment outcome. Korean J Pediatr 2014;57:125-34.
  22. Vlachos A, Klein GW, Lipton JM. The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia. J Pediatr Hematol Oncol 2001;23:377-82.
  23. Kim SK, Ahn HS, Back HJ, Cho B, Choi EJ, Chung NG, et al. Clinical and hematologic manifestations in patients with Diamond Blackfan anemia in Korea. Korean J Hematol 2012;47:131-5.
  24. Boria I, Garelli E, Gazda HT, Aspesi A, Quarello P, Pavesi E, et al. The ribosomal basis of Diamond-Blackfan Anemia: mutation and database update. Hum Mutat 2010;31:1269-79.
  25. Konno Y, Toki T, Tandai S, Xu G, Wang R, Terui K, et al. Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia. Haematologica 2010;95:1293-9.
  26. Chae H, Park J, Lee S, Kim M, Kim Y, Lee JW, et al. Ribosomal protein mutations in Korean patients with Diamond-Blackfan anemia. Exp Mol Med 2014;46:e88.
  27. Dutt S, Narla A, Lin K, Mullally A, Abayasekara N, Megerdichian C, et al. Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood 2011;117:2567-76.
  28. Campagnoli MF, Garelli E, Quarello P, Carando A, Varotto S, Nobili B, et al. Molecular basis of Diamond-Blackfan anemia: new findings from the Italian registry and a review of the literature. Haematologica 2004;89:480-9.
  29. Willig TN, Niemeyer CM, Leblanc T, Tiemann C, Robert A, Budde J, et al. Identification of new prognosis factors from the clinical and epidemiologic analysis of a registry of 229 Diamond-Blackfan anemia patients. DBA group of Societe d'Hematologie et d'Immunologie Pediatrique (SHIP), Gesellshaft fur Padiatrische Onkologie und Hamatologie (GPOH), and the European Society for Pediatric Hematology and Immunology (ESPHI). Pediatr Res 1999;46:553-61.
  30. Orfali KA, Ohene-Abuakwa Y, Ball SE. Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity. Br J Haematol 2004;125:243-52.
  31. Sankaran VG, Ghazvinian R, Do R, Thiru P, Vergilio JA, Beggs AH, et al. Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia. J Clin Invest 2012;122:2439-43.
  32. Landowski M, O'Donohue MF, Buros C, Ghazvinian R, Montel-Lehry N, Vlachos A, et al. Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond-Blackfan anemia. Hum Genet 2013;132:1265-74.
  33. Vlachos A, Rosenberg PS, Atsidaftos E, Alter BP, Lipton JM. Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry. Blood 2012;119:3815-9.
  34. Burroughs L, Woolfrey A, Shimamura A. Shwachman-Diamond syndrome: a review of the clinical presentation, molecular pathogenesis, diagnosis, and treatment. Hematol Oncol Clin North Am 2009;23:233-48.
  35. Dror Y. Shwachman-Diamond syndrome. Pediatr Blood Cancer 2005;45:892-901.
  36. Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, et al. Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nat Genet 2003;33:97-101.
  37. Ganapathi KA, Austin KM, Lee CS, Dias A, Malsch MM, Reed R, et al. The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA. Blood 2007;110:1458-65.
  38. Myers KC, Bolyard AA, Otto B, Wong TE, Jones AT, Harris RE, et al. Variable clinical presentation of Shwachman-Diamond syndrome: update from the North American Shwachman-Diamond Syndrome Registry. J Pediatr 2014;164:866-70.
  39. Manroe BL, Weinberg AG, Rosenfeld CR, Browne R. The neonatal blood count in health and disease. I. Reference values for neutrophilic cells. J Pediatr 1979;95:89-98.
  40. Schelonka RL, Yoder BA, desJardins SE, Hall RB, Butler J. Peripheral leukocyte count and leukocyte indexes in healthy newborn term infants. J Pediatr 1994;125:603-6.
  41. Zeidler C, Germeshausen M, Klein C, Welte K. Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) mutations in severe congenital neutropenia. Br J Haematol 2009;144:459-67.
  42. Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genet 1999;23:433-6.
  43. Ancliff PJ, Gale RE, Liesner R, Hann IM, Linch DC. Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease. Blood 2001; 98:2645-50.
  44. Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schaffer AA, et al. HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat Genet 2007;39:86-92.
  45. Boztug K, Appaswamy G, Ashikov A, Schaffer AA, Salzer U, Diestelhorst J, et al. A syndrome with congenital neutropenia and mutations in G6PC3. N Engl J Med 2009;360:32-43.
  46. Ancliff PJ, Blundell MP, Cory GO, Calle Y, Worth A, Kempski H, et al. Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia. Blood 2006;108:2182-9.
  47. Person RE, Li FQ, Duan Z, Benson KF, Wechsler J, Papadaki HA, et al. Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2. Nat Genet 2003;34:308-12.
  48. Dong F, Dale DC, Bonilla MA, Freedman M, Fasth A, Neijens HJ, et al. Mutations in the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia. Leukemia 1997;11:120-5.
  49. Lee ST, Yoon HS, Kim HJ, Lee JH, Park JH, Kim SH, et al. A novel mutation Ala57Val of the ELA2 gene in a Korean boy with severe congenital neutropenia. Ann Hematol 2009;88:593-5.
  50. Shim YJ, Kim HJ, Suh JS, Lee KS. Novel ELANE gene mutation in a Korean girl with severe congenital neutropenia. J Korean Med Sci 2011;26:1646-9.
  51. Park J, Kim M, Lim J, Kim Y, Cho B, Park YJ, et al. Molecular analysis of two cases of severe congenital neutropenia. Korean J Lab Med 2010;30:111-6.

Cited by

  1. Ribosomopathies: Global process, tissue specific defects vol.3, pp.1, 2015, https://doi.org/10.1080/21675511.2015.1025185
  2. Neonatal manifestations of inherited bone marrow failure syndromes vol.21, pp.1, 2014, https://doi.org/10.1016/j.siny.2015.12.003
  3. A newborn with very rare von Voss-Cherstvoy syndrome: a case report vol.9, pp.None, 2014, https://doi.org/10.2147/imcrj.s108746
  4. Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Genetic Rare Diseases in Children vol.23, pp.2, 2014, https://doi.org/10.15264/cpho.2016.23.2.133
  5. Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes vol.96, pp.8, 2017, https://doi.org/10.1007/s00277-017-3041-7
  6. Identification of potential pathogenic genes associated with osteoporosis vol.6, pp.12, 2017, https://doi.org/10.1302/2046-3758.612.bjr-2017-0102.r1