title: The gamma-crystallins and human cataracts: a puzzle made clearer.
abstract: 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.
authors.affiliation: Eye Research Institute of Canada, Toronto, Ontario, Canada. eheon@playfair.utoronto.ca
authors.forename: E
authors.initials: E
authors.lastname: Héon
authors.forename: M
authors.initials: M
authors.lastname: Priston
authors.forename: D F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: G D
authors.initials: GD
authors.lastname: Billingsley
authors.forename: P O
authors.initials: PO
authors.lastname: Girard
authors.forename: N
authors.initials: N
authors.lastname: Lubsen
authors.forename: F L
authors.initials: FL
authors.lastname: Munier
mesh_terms: D000595:Amino Acid Sequence; D002386:Cataract / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D003459:Crystallins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D003459:Crystallins