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Congenital dyserythropoietic anemia types Ib, II, and III: novel variants in the CDIN1 gene and functional study of a novel variant in the KIF23 gene

Annals of Hematology volume 100, pages 353–364 (2021)Cite this article

Abstract

Congenital dyserythropoietic anemias (CDA) are disorders characterized by ineffective erythropoiesis and morphological anomalies in erythrocytes and erythroblasts. The purpose of this study is to identify the gene variants in patients diagnosed with CDA. We analyzed five unrelated patients and two siblings with a targeted panel of genes to CDA: CDAN1, CDIN1, SEC23B, KIF23, KLF1, and GATA1 genes. We found three novel variants in the CDIN1 gene (p.Leu136Val, p.Tyr247Cys, and p.Ile273Thr), four known variants in the SEC23B gene (p.Arg14Trp, p.Arg554Ter, p.Asp239Gly, and p.Ser436Leu), and one novel variant in the KIF23 gene (p.Leu945Trpfs*31). The in silico analysis of novel variants predict that they are pathogenic and, the in vitro study confirms the functional impact of the KIF23 variant on the protein location.

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Funding

The genetic study was funded by a Spanish grant from “Fundación Investigación Biomédica Mutua Madrileña, 2016-0084,” and the functional study was funded by a Spanish grant from “Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), programa de fomento I+D+I, proyectos de investigación clínica, 2019-0040.”

Author information

Affiliations

  1. Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain

    Manuel Méndez, María Isabel Moreno-Carralero & María José Morán-Jiménez

  2. Servicio de Hematología, Complejo Hospitalario Insular-Materno Infantil, Las Palmas de Gran Canaria, Spain

    Valeria L. Peri & José M. Bosch-Benítez

  3. Servicio de Anatomía Patológica, Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria, Spain

    Rafael Camacho-Galán

  4. Servicio de Pediatría, Sección de Oncología y Hematología Pediátricas y del Adolescente, Hospital Materno-Infantil Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain

    Jorge Huerta-Aragonés

  5. Servicio Hematología, Hospital Móstoles, Madrid, Spain

    Jorge Sánchez-Calero-Guilarte

  6. Servicio de Hematología y Hemoterapia, Hospital Materno Infantil, Badajoz, Spain

    María Belén Moreno-Risco

  7. Servicio de Hematología, Fundación Jiménez Díaz, Grupo de Hematología Experimental, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain

    Juan Manuel Alonso-Domínguez

Authors
  1. Manuel Méndez
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  2. María Isabel Moreno-Carralero
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  3. Valeria L. Peri
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  4. Rafael Camacho-Galán
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  5. José M. Bosch-Benítez
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  6. Jorge Huerta-Aragonés
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  8. María Belén Moreno-Risco
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  9. Juan Manuel Alonso-Domínguez
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  10. María José Morán-Jiménez
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Contributions

MM performed the in vitro study, analyzed the results, and revised the article. MCMI performed the genetic study. PVL, BBJM, HAJ, SCGJ, MRMB, and ADJM diagnosed and cared for the patients, and revised the article. CGR performed the electronic microscopy study of patient 6a. MJMJ designed the genetic and in vitro studies, analyzed the results, and wrote the article.

Corresponding author

Correspondence to María José Morán-Jiménez.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethics approval

The Research Ethics Committee of the Hospital Universitario 12 de Octubre, Madrid, Spain, approved the genetic study. Written informed consent to perform the genetic analysis was according to the local guidelines (Ley de Investigación Biomédica 14/2007, Ley Orgánica de Protección de Datos y Garantía de Derechos Digitales 3/2018) and to the General Data Protection Regulation of the European Parliament and of the Council 2016/679.

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Patients were informed by the hematologists and gave their written consent.

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Information of all patients were anonymized and the submission does not include images or data that may identify the person.

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Méndez, M., Moreno-Carralero, M.I., Peri, V.L. et al. Congenital dyserythropoietic anemia types Ib, II, and III: novel variants in the CDIN1 gene and functional study of a novel variant in the KIF23 gene. Ann Hematol 100, 353–364 (2021). https://doi.org/10.1007/s00277-020-04319-5

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Keywords

  • CDA types Ib
  • II and III. CDIN1
  • SEC23B and KIF23 genes