The gamma-crystallins and human cataracts: a puzzle made clearer

Am J Hum Genet. 1999 Nov;65(5):1261-7. doi: 10.1086/302619.


Despite the fact that cataracts constitute the leading cause of blindness worldwide, the mechanisms of lens opacification remain unclear. We recently mapped the aculeiform cataract to the gamma-crystallin locus (CRYG) on chromosome 2q33-35, and mutational analysis of the CRYG-genes cluster identified the aculeiform-cataract mutation in exon 2 of gamma-crystallin D (CRYGD). This mutation occurred in a highly conserved amino acid and could be associated with an impaired folding of CRYGD. During our study, we observed that the previously reported Coppock-like-cataract mutation, the first human cataract mutation, in the pseudogene CRYGE represented a polymorphism seen in 23% of our control population. Further analysis of the original Coppock-like-cataract family identified a missense mutation in a highly conserved segment of exon 2 of CRYGC. These mutations were not seen in a large control population. There is no direct evidence, to date, that up-regulation of a pseudogene causes cataracts. To our knowledge, these findings are the first evidence of an involvement of CRYGC and support the role of CRYGD in human cataract formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cataract / ethnology
  • Cataract / genetics*
  • Cataract / pathology
  • Crystallins / genetics*
  • DNA Mutational Analysis
  • Female
  • Haplotypes
  • Humans
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid


  • Crystallins

Associated data

  • GENBANK/K03003
  • GENBANK/K03005
  • GENBANK/K03006
  • GENBANK/K03008
  • GENBANK/M19364