title: Hereditary hyperferritinaemia/ cataract syndrome.
abstract: In mammalian cells, cellular iron homeostasis is maintained by the co-ordinated regulation of transferrin receptor and ferritin synthesis that occurs at the translational level. This regulation is mediated by iron-responsive elements (IREs) that are found within the untranslated regions (UTRs) of mRNA and by cytoplasmic mRNA-binding proteins, known as iron regulatory proteins (IRPs). When cellular iron is scarce, IRPs are available for binding the 5' IRE of ferritin mRNA, initiation of translation is prevented and ferritin synthesis is inhibited. By contrast, the presence of abundant intracellular iron prevents binding of the IRPs to the 5' IRE and allows efficient mRNA translation to proceed. Hereditary hyperferritinaemia/cataract syndrome (HHCS) arises as a result of various point mutations or deletions within a protein binding sequence in the 5'-UTR of the L-ferritin mRNA, which results in increased efficiency of L-ferritin translation. Each unique mutation confers a characteristic degree of hyperferritinaemia and severity of cataract in affected individuals. This exemplifies a new paradigm in which mutations in mRNA cis-acting elements may be responsible for phenotypic variability in disease states.
authors.affiliation: Department of Hematology, University of Pavia Medical School, IRCCS Policlinico S. Matteo, Piazzale Golgi 2, 27100 Pavia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D002386:Cataract / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D005192:Family Health; D005293:Ferritins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019189:Iron Metabolism Disorders / Q000150:complications* / Q000235:genetics; D009154:Mutation; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D005293:Ferritins