Skip to main content
SpringerLink
Log in

Compound heterozygosity for two novel mutations of the SEC23B gene in congenital dyserythropoietic anemia type II

  • Case Report
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Congenital dyserythropoietic anemia type II (CDA II), a rare genetic disorder, results from SEC23B gene mutations according to previous studies. Here, we present a case of CDA II involving two novel pathogenic mutations of SEC23B that have not previously been reported. The patient suffered from jaundice, tea-colored urine, and weakness. Laboratory data indicated moderately decreased hemoglobin, iron overload, and abnormal erythroblast morphology. Therefore, a diagnosis of CDA II was considered. Peripheral blood samples were used to perform whole exome sequencing, and the results showed compound heterozygosity of the SEC23B gene with the following mutations: c.1162T>A (p.F388I) and c.1603delC (p.R535del). The mutant proteins were predicted to be deleterious and resulted in decreased structural stability. PyMOL software was used to analyze the structural change caused by the p.F388I missense mutation, and the results indicated a deficiency in π–π interactions. In conclusion, our report extends the mutation spectrum of SEC23B in the diagnosis of CDA II.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data accessibility

All study data, including raw and analyzed data and materials, will be available from the corresponding author upon reasonable request.

References

  1. Wickramasinghe SN, Wood WG. Advances in the understanding of the congenital dyserythropoietic anaemias. Br J Haematol. 2005;131(4):431–46. https://doi.org/10.1111/j.1365-2141.2005.05757.x.

    Article  CAS  PubMed  Google Scholar 

  2. Kamiya T, Manabe A. Congenital dyserythropoietic anemia. Int J Hematol. 2010;92(3):432–8. https://doi.org/10.1007/s12185-010-0667-9.

    Article  PubMed  Google Scholar 

  3. Bianchi P, Fermo E, Vercellati C, Boschetti C, Barcellini W, Iurlo A, et al. Congenital dyserythropoietic anemia type II (CDAII) is caused by mutations in the SEC23B gene. Hum Mutat. 2009;30(9):1292–8. https://doi.org/10.1002/humu.21077.

    Article  CAS  PubMed  Google Scholar 

  4. Gasparini P, Miraglia DGE, Delaunay J, Totaro A, Granatiero M, Melchionda S, et al. Localization of the congenital dyserythropoietic anemia II locus to chromosome 20q112 by genomewide search. Am J Hum Genet. 1997;61(5):1112–6. https://doi.org/10.1086/301609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Schwarz K, Iolascon A, Verissimo F, Trede NS, Horsley W, Chen W, et al. Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II. Nat Genet. 2009;41(8):936–40. https://doi.org/10.1038/ng.405.

    Article  CAS  PubMed  Google Scholar 

  6. Bianchi P, Schwarz K, Högel 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(4):696–704. https://doi.org/10.1111/bjh.14271.

    Article  CAS  PubMed  Google Scholar 

  7. Russo R, Esposito MR, Asci R, Gambale A, Perrotta S, Ramenghi U, et al. Mutational spectrum in congenital dyserythropoietic anemia type II: Identification of 19 novel variants in SEC23B gene. Am J Hematol. 2010;85(12):915–20. https://doi.org/10.1002/ajh.21866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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(10):E169–75. https://doi.org/10.1002/ajh.23800.

    Article  PubMed  Google Scholar 

  9. Heimpel H, Matuschek A, Ahmed M, Bader-Meunier B, Colita A, Delaunay J, et al. Frequency of congenital dyserythropoietic anemias in Europe. Eur J Haematol. 2010;85(1):20–5.

    PubMed  Google Scholar 

  10. Iolascon A, Heimpel H, Wahlin A, Tamary H. Congenital dyserythropoietic anemias: molecular insights and diagnostic approach. Blood. 2013;122(13):2162–6. https://doi.org/10.1182/blood-2013-05-468223.11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Amir A, Dgany O, Krasnov T, Resnitzky P, Mor-Cohen R, Bennett M, et al. E109K is a SEC23B founder mutation among israeli moroccan jewish patients with congenital dyserythropoietic anemia type II. Acta Haematol-Basel. 2011;125(4):202–7. https://doi.org/10.1159/000322948.

    Article  Google Scholar 

  12. Renella R. Progress in the congenital dyserythropoietic anemias: juicy but high-hanging fruits? Am J Hematol. 2010;85(12):913–4. https://doi.org/10.1002/ajh.21900.

    Article  CAS  PubMed  Google Scholar 

  13. Iolascon A, Russo R, Esposito MR, Asci R, Piscopo C, Perrotta S, et al. Molecular analysis of 42 patients with congenital dyserythropoietic anemia type II: new mutations in the SEC23B gene and a search for a genotype-phenotype relationship. Haematologica. 2010;95(5):708–15. https://doi.org/10.3324/haematol.2009.014985.

    Article  CAS  PubMed  Google Scholar 

  14. Heimpel H, Anselstetter V, Chrobak L, Denecke J, Einsiedler B, Gallmeier K, et al. Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation. Blood. 2003;102(13):4576–81. https://doi.org/10.1182/blood-2003-02-0613.

    Article  CAS  PubMed  Google Scholar 

  15. Heimpel H. Congenital dyserythropoietic anemias: epidemiology, clinical significance, and progress in understanding their pathogenesis. Ann Hematol. 2004. https://doi.org/10.1007/s00277-004-0892-5.

    Article  PubMed  Google Scholar 

  16. Miano M, Eikema D, Aljurf M, van Veer PJ, Öztürk G, Wölfl M, et al. Stem cell transplantation for congenital dyserythropoietic anemia: an analysis from the European society for blood and marrow transplantation. Haematologica. 2019;104(8):e335–9. https://doi.org/10.3324/haematol.2018.206623.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ma H, Marti-Gutierrez N, Park S, Wu J, Lee Y, Suzuki K, et al. Correction of a pathogenic gene mutation in human embryos. Nature. 2017;548(7668):413–9. https://doi.org/10.1038/nature23305.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The authors would like to acknowledge support from Zhongshan Social Development Tackling Plan (2016B1023), and the authors thank Zhecun Wang for performing the protein structure analysis using PyMOL software.

Author information

Authors and Affiliations

  1. Department of Hematology, Affiliated Zhongshan Hospital, Sun Yat-Sen University, No. 2 Sun-wen Dong Road, Zhongshan, 528403, China

    Shanshan Chen, Ziwen Guo, Yongbin Ye & Guinian Huang

  2. Department of Laboratory Medicine, Affiliated Zhongshan Hospital, Sun Yat-Sen University, Zhongshan, Guangdong, China

    Shanhong Yang

Authors
  1. Shanshan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ziwen Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yongbin Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shanhong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guinian Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guinian Huang.

Ethics declarations

Informed consent

Written informed consent was obtained from the patient for clinical diagnosis and research purposes.

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 554 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, S., Guo, Z., Ye, Y. et al. Compound heterozygosity for two novel mutations of the SEC23B gene in congenital dyserythropoietic anemia type II. Int J Hematol 114, 390–394 (2021). https://doi.org/10.1007/s12185-021-03155-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-021-03155-1

Keywords

Search

Navigation