title: Ferritin crystal cataracts in hereditary hyperferritinemia cataract syndrome.
abstract: OBJECTIVE
  Hereditary hyperferritinemia cataract syndrome (HHCS) is a genetic disease defined by cataracts, hyperferritinemia, and ferritin light-chain (L-ferritin) gene mutations. HHCS was diagnosed in this study in one of the first families known to be affected in the United States, and the basis of lens opacities in HHCS was determined.
  
  
  METHODS
  DNA amplification and sequencing of the human L-ferritin gene was used for mutation detection. RNA electrophoretic mobility shift analysis was performed to demonstrate functional consequences of a new mutation. Opacities were characterized by immunohistochemical and electron microscopic analyses of human HHCS lens aspirate.
  
  
  RESULTS
  HHCS was diagnosed in five members of one family who had all three hallmark features: hyperferritinemia, a prominent cataract or history, and the finding of a novel mutation in the L-ferritin gene (C33T). This mutation interferes with function of the L-ferritin transcript in an RNA gel shift assay. Light-diffracting crystalline deposits were present in cataractous lenses from two affected family members but not in control lenses. Immunohistochemical analysis showed strong anti-L-ferritin reactivity in the crystalline deposits. Analysis of these deposits by transmission electron microscopy with fast Fourier transformation demonstrated macromolecular crystalline structure of the deposits. The data were consistent with a face-centered cubic crystal having a unit crystal cell size of 17 nm, both findings characteristic of ferritin crystals grown in vitro.
  
  
  CONCLUSIONS
  HHCS cataract is due to numerous small opacities, predominantly in the lens cortex, that are light-diffracting ferritin crystals. Patients with HHCS may be recognized by a family history of cataracts and hyperferritinemia without increased serum iron.
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. brooksda@mail.med.upenn.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Brooks
authors.forename: Katia
authors.initials: K
authors.lastname: Manova-Todorova
authors.forename: Jennifer
authors.initials: J
authors.lastname: Farmer
authors.forename: Lioba
authors.initials: L
authors.lastname: Lobmayr
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wilson
authors.forename: Ralph C
authors.initials: RC
authors.lastname: Eagle
authors.forename: Tim G
authors.initials: TG
authors.lastname: St  Pierre
authors.forename: Dwight
authors.initials: D
authors.lastname: Stambolian
mesh_terms: D002386:Cataract / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003460:Crystallization; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005293:Ferritins / Q000097:blood* / Q000235:genetics*; D006801:Humans; D019189:Iron Metabolism Disorders / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D007908:Lens, Crystalline / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D013577:Syndrome
chemical_list: D005293:Ferritins