title: A point mutation in the bulge of the iron-responsive element of the L ferritin gene in two families with the hereditary hyperferritinemia-cataract syndrome.
abstract: The molecular basis for the recently described hereditary hyperferritinemia-cataract syndrome is the presence of a mutation in the iron-responsive element (IRE) of the L ferritin gene, located on chromosome 19q13.3-13.4. Two mutations have been reported so far, altering adjacent nucleotides in the IRE loop, in a region that has been extensively studied in vitro and shown to mediate high affinity interaction with the iron-responsive protein. In this report, we describe two families with a new mutation in the bulge of the IRE stem, and we show that this mutation alters the protein-binding affinity of the IRE in vitro to the same extent as the loop mutation. In addition, we present evidence that some variability in the age of onset of cataract can be associated with this genetic syndrome, probably because of additional genetic or environmental factors that modulate the penetrance of the L ferritin defect in the lens. We confirm that the patients do not have increased iron stores despite the persistence of elevated serum ferritin levels and that, accordingly, they do not tolerate well venesection therapy. Further studies will be necessary to elucidate the mechanism responsible for the onset of cataract.
authors.affiliation: Génétique et Pathologie Moléculaires de l'Hématopoièse, INSERM U409, Facult-e Xavier Bichat, Paris, France.
authors.forename: M E
authors.initials: ME
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Fargion
authors.forename: P
authors.initials: P
authors.lastname: Brissot
authors.forename: B
authors.initials: B
authors.lastname: Pellat
authors.forename: C
authors.initials: C
authors.lastname: Beaumont
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001052:Apoferritins; D001665:Binding Sites; D002386:Cataract / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics / Q000648:ultrastructure; D000075202:Contraindications; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005293:Ferritins / Q000097:blood / Q000235:genetics*; D005602:France / Q000453:epidemiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009690:Nucleic Acid Conformation; D010375:Pedigree; D018962:Phlebotomy; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid; D013577:Syndrome
chemical_list: D004247:DNA; D005293:Ferritins; D001052:Apoferritins; D007501:Iron