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 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.
Camaschella
C
C
Dipartimento di Scienze Cliniche e Biologiche, University of Turin, Italy. Camaschella@ope.net
Zecchina
G
G
Lockitch
G
G
Roetto
A
A
Campanella
A
A
Arosio
P
P
Levi
S
S
D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000097:blood / Q000235:genetics*; D002386:Cataract / Q000097:blood / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013577:Syndrome
D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D005293:Ferritins