New cases of hypochromic microcytic anemia due to mutations in the SLC11A2 gene and functional characterization of the G75R mutation
Autor/a
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
Fecha de publicación
2022ISSN
1422-0067
Resumen
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.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
Inglés
Materias (CDU)
61 - Medicina
Palabras clave
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
Páginas
13
Publicado por
MDPI
Colección
23
Publicado en
International Journal of Molecular Sciences
Citación
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
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© 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/).
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