C29G in the iron-responsive element of l-ferritin: a new mutation associated with hyperferritinemia-cataract

Hyperferritinemia-cataract syndrome (HHCS) is a dominant disorder characterized by high serum ferritin and early onset of bilateral cataract. The disorder is caused by mutations in the iron-responsive element (IRE) of l-ferritin, which disrupt the postranscriptional control of l-ferritin synthesis. Here, we report a new (C>G) mutation which affects base 29 in the loop (c.-169C>G), previously unrecognized as essential for the stem loop stability. The mutation was identified in two members of an Italian family. Computer modeling and electrophoretic mobility shift assay (EMSA) confirm a decreased affinity of the C29G IRE for IRPs control proteins.