A novel deletion of the l‐ferritin iron‐responsive element responsible for severe hereditary hyperferritinaemia–cataract syndrome

Summary. 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.

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