Novel mutations in the ferritin-L iron-responsive element that only mildly impair IRP binding cause hereditary hyperferritinaemia cataract syndrome
Autor/a
Luscieti, Sara
Tolle, Gabriele
Aranda, Jessica
Benet Campos, Carmen
Risse, Frank
Morán, Érica
Muckenthaler, Martina U.
Sánchez, Mayka
Data de publicació
2013ISSN
1750-1172
Resum
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.
Tipus de document
Article
Versió del document
Versió publicada
Llengua
English
Matèries (CDU)
57 - Biologia
Paraules clau
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
Pàgines
10
Publicat per
Springer Nature
Col·lecció
8;
Publicat a
Orphanet Journal of Rare Diseases
Citació
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
Aquest element apareix en la col·lecció o col·leccions següent(s)
- Ciències de la Salut [738]
Drets
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.
Excepte que s'indiqui una altra cosa, la llicència de l'ítem es descriu com https://creativecommons.org/licenses/by/2.0