New cases of hypochromic microcytic anemia due to mutations in the SLC11A2 gene and functional characterization of the G75R mutation
Author
Romero-Cortadellas, Lídia
Hernández, Gonzalo
Ferrer-Cortès, Xènia
Zalba-Jadraque, Laura
Fuster, José Luis
Bermúdez-Cortés, Mar
Galera-Miñarro, Ana María
Pérez-Montero, Santiago
Tornador, Cristian
Sánchez, Mayka
Publication date
2022ISSN
1422-0067
Abstract
Divalent metal-iron transporter 1 (DMT1) is a mammalian iron transporter encoded by the SLC11A2 gene. DMT1 has a vital role in iron homeostasis by mediating iron uptake in the intestine and kidneys and by recovering iron from recycling endosomes after transferrin endocytosis. Mutations in SLC11A2 cause an ultra-rare hypochromic microcytic anemia with iron overload (AHMIO1), which has been described in eight patients so far. Here, we report two novel cases of this disease. The first proband is homozygous for a new SLC11A2 splicing variant (c.762 + 35A > G), becoming the first ever patient reported with a SLC11A2 splicing mutation in homozygosity. Splicing studies performed in this work confirm its pathogenicity. The second proband harbors the previously reported DMT1 G75R mutation in homozygosis. Functional studies with the G75R mutation in HuTu 80 cells demonstrate that this mutation results in improper DMT1 accumulation in lysosomes, which correlates with a significant decrease in DMT1 levels in patient-derived lymphoblast cell lines (LCLs). We also suggest that recombinant erythropoietin would be an adequate therapeutic approach for AHMIO1 patients as it improves their anemic state and may possibly contribute to mobilizing excessive hepatic iron.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
DMT1
Anèmia microcítica
Sobrecàrrega de ferro
SLC11A2
Mutació
EPO
DMT1
Anemia microcítica
Sobrecarga de hierro
SLC11A2
Mutación
OEP
DMT1
Microcytic anemia
Iron overload
SLC11A2
Mutation
EPO
Pages
13
Publisher
MDPI
Collection
23
Is part of
International Journal of Molecular Sciences
Citation
Romero-Cortadellas, Lídia; Hernández, Gonzalo; Ferrer-Cortès, Xènia [et al.]. New cases of hypochromic microcytic anemia due to mutations in the SLC11A2 gene and functional characterization of the G75R mutation. International Journal of Molecular Sciences, 2022, 23(8), 4406. Disponible en: <https://www.mdpi.com/1422-0067/23/8/4406>. Fecha de acceso: 23 ene. 2024. DOI: 10.3390/ijms23084406
This item appears in the following Collection(s)
- Comunicació [97]
Rights
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/