A juvenile-onset, progressive cataract locus on chromosome 3q21-q22 is associated with a missense mutation in the beaded filament structural protein-2

Am J Hum Genet. 2000 Apr;66(4):1426-31. doi: 10.1086/302871. Epub 2000 Mar 22.


Juvenile-onset cataracts are distinguished from congenital cataracts by the initial clarity of the lens at birth and the gradual development of lens opacity in the second and third decades of life. Genomewide linkage analysis in a multigenerational pedigree, segregating for autosomal dominant juvenile-onset cataracts, identified a locus in chromosome region 3q21.2-q22.3. Because of the proximity of the gene coding for lens beaded filament structural protein-2 (BFSP2) to this locus, we screened for mutations in the coding sequence of BFSP2. We observed a unique C-->T transition, one that was not observed in 200 normal chromosomes. We predicted that this led to a nonconservative R287W substitution in exon 4 that cosegregated with cataracts. This mutation alters an evolutionarily conserved arginine residue in the central rod domain of the intermediate filament. On consideration of the proposed function of BFSP2 in the lens cytoskeleton, it is likely that this alteration is the cause of cataracts in the members of the family we studied. This is the first example of a mutation in a noncrystallin structural gene that leads to a juvenile-onset, progressive cataract.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Animals
  • Cataract / epidemiology*
  • Cataract / genetics*
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 3 / genetics*
  • Eye Proteins / chemistry
  • Eye Proteins / genetics*
  • Female
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease / genetics
  • Haplotypes / genetics
  • Humans
  • Intermediate Filament Proteins / chemistry
  • Intermediate Filament Proteins / genetics*
  • Lod Score
  • Male
  • Middle Aged
  • Mutation, Missense / genetics*
  • Pedigree
  • Penetrance
  • Sequence Alignment


  • Eye Proteins
  • Intermediate Filament Proteins
  • phakinin