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

Mayka Sánchez⁴  Martina U Muckenthaler¹  Érica Morán⁴  Frank Risse²  Carmen Benet Campos³  Jessica Aranda⁴  Gabriele Tolle¹  Sara Luscieti⁴ 

[1] Department of Pediatric Oncology, Hematology, and Immunology, University Hospital of Heidelberg, Heidelberg, Germany;Praxis für Hämatologie- Onkologie Rhein Ahr, Remagen, Germany;Servicio de hematología y hemoterapia, Hospital Arnau de Vilanova, Valencia, Spain;Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Ctra. de Can Ruti, Camí de les Escoles s/n, 08916, Badalona, Barcelona, Spain

关键词: Bilateral cataracts;    IRP/IRE regulatory system;    Iron metabolism;    Serum ferritin;   

Others  :  864114
DOI  :  10.1186/1750-1172-8-30

 received in 2012-10-23, accepted in 2013-02-14,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Luscieti et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

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