Genetic studies by Sanger
Hereditary Hyperferritinemia with cataracts Syndrome (HHCS, exon 1 FTL) (Code 20050)
Ferritin is the protein responsible for the storage and intracellular distribution of iron. It consists of two subunits called L-ferritin and H-ferritin. The synthesis of these subunits is controlled by regulatory proteins called iron regulatory proteins (IRPs) that bind to a regulatory element called the iron-responsive element (IRE) present in the 5’UTR of the mRNA of each of these two subunits.
Hyperferritinemia hereditary cataract syndrome (HHCS) (OMIM # 600886) is characterized by elevated levels of serum ferritin without iron overload with congenital cataracts and an autosomal dominant inheritance. Excess production of ferritin is due to mutations in the regulatory element called the iron-responsive element (IRE) in ferritin L (FTL). Multiple mutations in the IRE of Ferritin L have been described as causing HHCS (Luscieti et al., 2013). Excessive ferritin accumulates in the ocular lens which leads to the development of cataracts. The degree of involvement varies even among individuals with the same mutation. A correct genetic diagnosis of this disease is important, since it is often confused with hereditary hemochromatosis due to the high levels of serum ferritin present in both diseases. This syndrome was first described in 1995 (OMIM # 600886).
- Beaumont, C., Leneuve, P., Devaux, I., Scoazec, J.-Y., Berthier, M., Loiseau, M.-N., Grandchamp, B., Bonneau, D. Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract. Nature Genet. 11: 444-446, 1995. [PubMed: 7493028]
- Girelli, D., Olivieri, O., De Franceschi, L., Corrocher, R., Bergamaschi, G., Cazzola, M. A linkage between hereditary hyperferritinaemia not related to iron overload and autosomal dominant congenital cataract. Brit. J. Haemat. 90: 931-934, 1995. [PubMed: 7669675]
- Luscieti S, Tolle G, Aranda J, Campos CB, Risse F, Morán É, Muckenthaler MU,Sánchez M. Novel mutations in the ferritin-L iron-responsive element that only mildly impair IRP binding cause hereditary hyperferritinaemia cataract syndrome. Orphanet J Rare Dis. 8:30, 2013. [PubMed PMID: 23421845