title: A novel deletion of the L-ferritin iron-responsive element responsible for severe hereditary hyperferritinaemia-cataract syndrome.
abstract: In the last few years, mutations that cause disease through increased efficiency of mRNA translation have been discovered. Hereditary hyperferritinaemia-cataract syndrome (HHCS) arises from various point mutations or deletions within the iron-responsive element (IRE) in the 5'-UTR of the L-ferritin mRNA. Each unique mutation confers a characteristic degree of hyperferritinaemia and severity of cataract in affected individuals. We report a novel six-nucleotide deletion identified in an Italian family presenting with elevated serum ferritin and early onset bilateral cataract. This deletion involves a sequence with a TCT repetition and may have occurred through a mechanism of slippage mispairing. Because of the above repetition, the observed mutation can be interpreted as deletion 22-27, 23-28, 24-29 or 25-30. Structural modelling predicted an IRE stem modification that is expected to markedly reduce the binding to iron-regulatory proteins. A double-gradient denaturing gradient gel electrophoresis (DG-DGGE) method easily detected the above deletion.
authors.affiliation: Division of Haematology, University of Pavia Medical School, IRCCS Policlinico S. Matteo, 27100 Pavia, Italy. m.cazzola@iol.it
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Barbara
authors.initials: B
authors.lastname: Foglieni
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bergamaschi
authors.forename: Sonia
authors.initials: S
authors.lastname: Levi
authors.forename: Mario
authors.initials: M
authors.lastname: Lazzarino
authors.forename: Paolo
authors.initials: P
authors.lastname: Arosio
mesh_terms: D000328:Adult; D002386:Cataract / Q000097:blood / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005293:Ferritins / Q000097:blood* / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D013577:Syndrome
chemical_list: D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D016601:RNA-Binding Proteins; D005293:Ferritins