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

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