Advertisement

International Journal of Hematology

, Volume 108, Issue 3, pp 306–311 | Cite as

Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia

  • Motoharu Hamada
  • Sayoko Doisaki
  • Yusuke Okuno
  • Hideki Muramatsu
  • Asahito Hama
  • Nozomu Kawashima
  • Atsushi Narita
  • Nobuhiro Nishio
  • Kenichi Yoshida
  • Hitoshi Kanno
  • Atsushi Manabe
  • Takashi Taga
  • Yoshiyuki Takahashi
  • Satoru Miyano
  • Seishi Ogawa
  • Seiji Kojima
Original Article

Abstract

Congenital dyserythropoietic anemia (CDA) is a heterogeneous group of rare congenital disorders characterized by ineffective erythropoiesis and dysplastic changes in erythroblasts. Diagnosis of CDA is based primarily on the morphology of bone marrow erythroblasts; however, genetic tests have recently become more important. Here, we performed genetic analysis of 10 Japanese patients who had been diagnosed with CDA based on laboratory findings and morphological characteristics. We examined 10 CDA patients via central review of bone marrow morphology and genetic analysis for congenital bone marrow failure syndromes. Sanger sequencing for CDAN1, SEC23B, and KLF1 was performed for all patients. We performed whole-exome sequencing in patients without mutation in these genes. Three patients carried pathogenic CDAN1 mutations, whereas no SEC23B mutations were identified in our cohort. WES unexpectedly identified gene mutations known to cause congenital hemolytic anemia in two patients: canonical G6PD p.Val394Leu mutation and SPTA1 p.Arg28His mutation. Comprehensive genetic analysis is warranted for more effective diagnosis of patients with suspected CDA.

Keywords

Congenital dyserythropoietic anemia Congenital hemolytic anemia Whole-exome analysis 

Notes

Acknowledgements

The authors would like to thank all the clinicians and the patients and families who made this study possible by providing clinical samples. The authors would also like to thank Yoshie Miura, Yuko Imanishi, and Hiroe Namizaki for their valuable assistance. The authors acknowledge the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine for technical support for next-generation sequencing.

Funding

This work was supported by the Research on Measures for Intractable Diseases Project from Ministry of Health, Labor, and Welfare and a Grant-in-Aid from the Ministry of Health, Labor, and Welfare of Japan (H23-TA012).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

References

  1. 1.
    Heimpel H, Wendt F. Congenital dyserythropoietic anemia with karyorrhexis and multinuclearity of erythroblasts. Helv Med Acta. 1968;34:103–15.PubMedGoogle Scholar
  2. 2.
    Fujino H, Doisaki S, Park YD, Hama A, Muramatsu H, Kojima S, et al. Congenital dyserythropoietic anemia type 1 with a novel mutation in the CDAN1 gene previously diagnosed as congenital hemolytic anemia. Int J Hematol. 2013;97:650–3.CrossRefPubMedGoogle Scholar
  3. 3.
    Iolascon A, Esposito MR, Russo R. Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach. Haematologica. 2012;97:1786–94.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ru Y, Liu G, Bai J, Dong S, Nie N, Zhang H, et al. Congenital dyserythropoietic anemia in China: a case report from two families and a review. Ann Hematol. 2014;93:773–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Kamiya T, Manabe A. Congenital dyserythropoietic anemia. Int J Hematol. 2010;92:432–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Iolascon A, Heimpel H, Wahlin A, Tamary H. Congenital dyserythropoietic anemias: molecular insights and diagnostic approach. Blood. 2013;122:2162–6.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Russo R, Gambale A, Langella C, Andolfo I, Unal S, Iolascon A. Retrospective cohort study of 205 cases with congenital dyserythropoietic anemia type II: definition of clinical and molecular spectrum and identification of new diagnostic scores. Am J Hematol. 2014;89:E169–75.CrossRefGoogle Scholar
  8. 8.
    Kunishima S, Okuno Y, Yoshida K, Shiraishi Y, Sanada M, Muramatsu H, et al. ACTN1 mutations cause congenital macrothrombocytopenia. Am J Hum Genet. 2013;92:431–8.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Dgany O, Avidan N, Delaunay J, Krasnov T, Shalmon L, Shalev H, et al. Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1. Am J Hum Genet. 2002;71:1467–74.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bianchi P, Schwarz K, Hogel J, Fermo E, Vercellati C, Grosse R, et al. Analysis of a cohort of 101 CDAII patients: description of 24 new molecular variants and genotype–phenotype correlations. Br J Haematol. 2016;175:696–704.CrossRefPubMedGoogle Scholar
  12. 12.
    Haija MA, Qian YW, Muthukumar A. Dyserythropoiesis in a child with pyruvate kinase deficiency and coexistent unilateral multicystic dysplastic kidney. Pediatr Blood Cancer. 2014;61:1463–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Roy NB, Wilson EA, Henderson S, Wray K, Babbs C, Okoli S, et al. A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias. Br J Haematol. 2016;175:318–30.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Muramatsu H, Okuno Y, Yoshida K, Shiraishi Y, Doisaki S, Narita A, et al. Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. Genet Med. 2017;19:796–802.CrossRefPubMedGoogle Scholar
  15. 15.
    Paw BH, Davidson AJ, Zhou Y, Li R, Pratt SJ, Lee C, et al. Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency. Nat Genet. 2003;34:59–64.CrossRefPubMedGoogle Scholar
  16. 16.
    Bader-Meunier B, Leverger G, Tchernia G, Schischmanoff O, Cynober T, Bernaudin F, et al. Clinical and laboratory manifestations of congenital dyserythropoietic anemia type I in a cohort of French children. J Pediatr Hematol Oncol. 2005;27:416–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Baines AJ, Banga JP, Gratzer WB, Linch DC, Huehns ER. Red cell membrane protein anomalies in congenital dyserythropoietic anaemia, type II (HEMP AS). Br J Haematol. 1982;50:563–74.CrossRefPubMedGoogle Scholar
  18. 18.
    Iolascon A, Andolfo I, Barcellini W, Corcione F, Garcon L, De Franceschi L, et al. Recommendations regarding splenectomy in hereditary hemolytic anemias. Haematologica. 2017;102:1304–13.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Beutler E, Westwood B, Prchal JT, Vaca G, Bartsocas CS, Baronciani L. New glucose-6-phosphate dehydrogenase mutations from various ethnic groups. Blood 1992;80:255–6.PubMedGoogle Scholar
  20. 20.
    Garbarz M, Lecomte MC, Feo C, Devaux I, Picat C, Lefebvre C, et al. Hereditary pyropoikilocytosis and elliptocytosis in a white French family with the spectrin alpha I/74 variant related to a CGT to CAT codon change (Arg to His) at position 22 of the spectrin alpha I domain. Blood. 1990;75:1691–8.PubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Motoharu Hamada
    • 1
  • Sayoko Doisaki
    • 1
  • Yusuke Okuno
    • 2
  • Hideki Muramatsu
    • 1
  • Asahito Hama
    • 1
  • Nozomu Kawashima
    • 1
  • Atsushi Narita
    • 1
  • Nobuhiro Nishio
    • 1
    • 2
  • Kenichi Yoshida
    • 3
  • Hitoshi Kanno
    • 4
  • Atsushi Manabe
    • 5
  • Takashi Taga
    • 6
  • Yoshiyuki Takahashi
    • 1
  • Satoru Miyano
    • 7
    • 8
  • Seishi Ogawa
    • 3
  • Seiji Kojima
    • 1
  1. 1.Department of PediatricsNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Center for Advanced Medicine and Clinical ResearchNagoya University HospitalNagoyaJapan
  3. 3.Department of Pathology and Tumor BiologyKyoto UniversityKyotoJapan
  4. 4.Department of Transfusion Medicine and Cell ProcessingTokyo Women’s Medical UniversityTokyoJapan
  5. 5.Department of PediatricsSt. Luke’s International HospitalTokyoJapan
  6. 6.Department of PediatricsShiga University of Medical ScienceOtsuJapan
  7. 7.Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical ScienceThe University of TokyoTokyoJapan
  8. 8.Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical ScienceThe University of TokyoTokyoJapan

Personalised recommendations