title: Hereditary hyperferritinemia-cataract syndrome in two large multigenerational American families.
abstract: OBJECTIVE
  Hereditary hyperferritinemia cataract syndrome (HHCS), an autosomal-dominant disorder characterized by hyperferritinemia and bilateral cataracts, is caused by mutations in the iron-responsive element of the ferritin light chain (FTL) gene. The purpose of this study is to describe the genotypic and phenotypic manifestations of HHCS observed in 2 large sets of unrelated American families.
  
  
  METHODS
  Forty-five patients were recruited from 2 unrelated families. Each underwent ophthalmological and general physical evaluation as well as laboratory testing of serum ferritin, iron, transferrin saturation, and total iron binding capacity. Serum DNA was evaluated for mutations by DNA amplification and sequencing of the FTL gene.
  
  
  RESULTS
  Numerous cortical and nuclear white opacities in a stellate pattern occurred in 22 affected individuals and were the only clinical manifestation of HHCS. Of the 22, 16 (73%) demonstrated >1.00 D of astigmatism. Genetic analysis revealed mutation G32A in Pedigree 1 and mutation G32T in Pedigree 2, both heterozygous and located in the iron-responsive element of the ferritin light chain mRNA. Serum ferritin levels of affected subjects ranged from 555 to 2,453 μg/L (normal range, 24-336 μg/L male, 11-307 μg/L female), with greater ferritin levels and more severe cataracts associated with mutation G32A.
  
  
  CONCLUSIONS
  Most clinical and genetic findings from these families are consistent with previous reports of HHCS. Astigmatism, previously not associated with HHCS, was present in the majority. Ferritin levels and age of cataract surgery varied among subjects with both FTL gene mutations, suggesting that phenotypic variability is modulated by other genetic or environmental factors.
authors: College of Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
authors: Julia
authors: J
authors: Shekunov
authors: Piet C
authors: PC
authors: de Groen
authors: Noralane M
authors: NM
authors: Lindor
authors: George G
authors: GG
authors: Klee
authors: Ross A
authors: RA
authors: Aleff
authors: Eric D
authors: ED
authors: Wieben
authors: Brian G
authors: BG
authors: Mohney
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001052:Apoferritins / Q000235:genetics*; D001251:Astigmatism / Q000235:genetics* / Q000473:pathology*; D002386:Cataract / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D002648:Child; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D019189:Iron Metabolism Disorders / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D014481:United States; D055815:Young Adult
chemical_list: C507433:FTL protein, human; D001052:Apoferritins