Novel mutations in the ferritin-L iron-responsive element that only mildly impair IRP binding cause hereditary hyperferritinaemia cataract syndrome
Author
Luscieti, Sara
Tolle, Gabriele
Aranda, Jessica
Benet Campos, Carmen
Risse, Frank
Morán, Érica
Muckenthaler, Martina U.
Sánchez, Mayka
Publication date
2013ISSN
1750-1172
Abstract
Background: Hereditary Hyperferritinaemia Cataract Syndrome (HHCS) is a rare autosomal dominant disease characterized by increased serum ferritin levels and early onset of bilateral cataract. The disease is caused by mutations in the Iron-Responsive Element (IRE) located in the 5′ untranslated region of L-Ferritin (FTL) mRNA, which post-transcriptionally regulates ferritin expression. Methods: We describe two families presenting high serum ferritin levels and juvenile cataract with novel mutations in the L-ferritin IRE. The mutations were further characterized by in vitro functional studies. Results: We have identified two novel mutations in the IRE of L-Ferritin causing HHCS: the Badalona +36C > U and the Heidelberg +52 G > C mutation. Both mutations conferred reduced binding affinity on recombinant Iron Regulatory Proteins (IPRs) in EMSA experiments. Interestingly, the Badalona +36C > U mutation was found not only in heterozygosity, as expected for an autosomal dominant disease, but also in the homozygous state in some affected subjects. Additionally we report an update of all mutations identified so far to cause HHCS. Conclusions: The Badalona +36C > U and Heidelberg +52 G > C mutations within the L-ferritin IRE only mildly alter the binding capacity of the Iron Regulatory Proteins but are still causative for the disease.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
57 - Biological sciences in general
Keywords
Mutacions
Ferro ferritina-L
Síndrome de cataracta d'hiperferritinèmia hereditària
Ferritina sèrica
Metabolisme del ferro
Sistema regulador IRP/IRE
Cataractes bilaterals
Hierro ferritina-L
Síndrome de catarata de hiperferritinemia hereditaria
Ferritina sérica
Metabolismo del hierro
Sistema regulador IRP/IRE
Cataratas bilaterales
Ferro ferritin-L
Hereditary hyperferritinemia cataract syndrome
Serum ferritin
Iron metabolism
IRP / IRE regulatory system
Bilateral cataracts
Pages
10
Publisher
Springer Nature
Collection
8;
Is part of
Orphanet Journal of Rare Diseases
Citation
Luscieti, Sara; Tolle, Gabriele; Aranda, Jessica [et al.]. Novel mutations in the ferritin-L iron-responsive element that only mildly impair IRP binding cause hereditary hyperferritinaemia cataract syndrome. Orphanet Journal of Rare Diseases, 2013, 8, 30. Disponible en: <https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-30>. Fecha de acceso: 18 ene. 2022. DOI: 10.1186/1750-1172-8-30
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- Ciències de la Salut [738]
Rights
This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/2.0