A new mutation (G51C) in the iron-responsive element (IRE) of L-ferritin associated with hyperferritinaemia-cataract syndrome decreases the binding affinity of the mutated IRE for iron-regulatory proteins

Br J Haematol. 2000 Mar;108(3):480-2. doi: 10.1046/j.1365-2141.2000.01920.x.

Abstract

Hereditary hyperferritinaemia-cataract syndrome is an autosomal dominant disorder characterized by a constitutively increased synthesis of L-ferritin in the absence of iron overload. The disorder is associated with point mutations in the iron-responsive element (IRE) of L-ferritin mRNA. We report a new mutation, G51C, identified in two members of a Canadian family, presenting a moderate increase in serum ferritin and a clinically silent bilateral cataract. Gel retardation assays showed that the binding of the mutated IRE to iron-regulatory proteins (IRPs) was reduced compared with the wild type. Structural modelling predicted that the G51C induces a rearrangement of base pairing at the lateral bulge of the IRE structure which is likely to modify IRE conformation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia / blood
  • Anemia / genetics*
  • Cataract / blood
  • Cataract / genetics*
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Ferritins / blood*
  • Humans
  • Iron-Regulatory Proteins
  • Iron-Sulfur Proteins / genetics*
  • Male
  • Middle Aged
  • Point Mutation*
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / genetics*
  • Sequence Analysis, DNA
  • Syndrome

Substances

  • Iron-Regulatory Proteins
  • Iron-Sulfur Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ferritins

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