title: Recurrent mutations in the iron regulatory element of L-ferritin in hereditary hyperferritinemia-cataract syndrome.
abstract: OBJECTIVE
  Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant disorder characterized by bilateral cataracts and increased serum and tissue L-ferritin, in the absence of iron overload. The deregulation of ferritin production is caused by heterogeneous mutations in the iron regulatory element (IRE) of L-ferritin that interfere with the binding of iron regulatory proteins.
  
  
  METHODS
  We have identified several patients from three unrelated Italian families with HHCS. Iron parameters were assessed by standard methods. The IRE element of L-ferritin was amplified by PCR using appropriate primers and directly sequenced.
  
  
  RESULTS
  Ferritin levels ranged from 918 microg/L to 2490 microg/L in the patients studied. In one family bilateral cataracts were diagnosed early in life, whereas in the others cataracts were diagnosed around 40-50 years. The female proband of family 3 presented with a severe iron deficiency anemia, which was unrecognized because of the increased ferritin values. Sequencing of the IRE element of L-ferritin in the probands of the three families identified three different nucleotide substitutions (+32 GAE A, +40 AAE G and +39 CT) in the IRE of L-ferritin. These mutations have already been reported in unrelated subjects of different ethnic origins.
  
  
  CONCLUSIONS
  Our findings are consistent with recurrent mutations associated with HHCS and underline the importance of this syndrome in the differential diagnosis of unexplained hyperferritinemia. In addition, the findings highlight the role played by transferrin saturation in the diagnosis of iron deficiency in these patients.
authors.affiliation: Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliera S. Luigi, Orbassano (TO), Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cicilano
authors.forename: G
authors.initials: G
authors.lastname: Zecchina
authors.forename: A
authors.initials: A
authors.lastname: Roetto
authors.forename: S
authors.initials: S
authors.lastname: Bosio
authors.forename: V
authors.initials: V
authors.lastname: Infelise
authors.forename: S
authors.initials: S
authors.lastname: Stefani
authors.forename: U
authors.initials: U
authors.lastname: Mazza
authors.forename: C
authors.initials: C
authors.lastname: Camaschella
mesh_terms: D000328:Adult; D002386:Cataract / Q000097:blood* / Q000235:genetics*; D005192:Family Health; D005260:Female; D005293:Ferritins / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D020218:Response Elements; D013577:Syndrome
chemical_list: D005293:Ferritins; D007501:Iron