Molecular analysis of hereditary hyperferritinemia-cataract syndrome in a large Basque family

Hereditary hyperferritinemia-cataract syndrome is a genetic condition chara cterized by constitutively increased serum ferritin values in the absence o f iron overload and by bilateral cataract. It has been demonstrated that mu tations in the stem loop structure of the iron regulatory element (IRE) loc ated in the 5'-untranslated region of the ferritin L-subunit gene (19q13.1) are responsible for the anomalous expression of this protein. Although not clearly explained, cataract formation seems secondary to the increased lev els of ferritin in the lens, We analyzed a large Basque family in order to identify possible germline alterations of the iron regulatory element of th e ferritin-l gene in affected individuals and first-degree relatives, All m embers of the family presented hyperferritinemia and cataract except a youn g child who had hyperferritinemia but did not present cataract. Sequence an alysis permitted the identification of an A40-->G mutation in all members, including this child. This could demonstrate that cataract formation is a c onsequence of ferritin accumulation in the lens.