Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract

Nat Genet. 2002 Jul;31(3):276-8. doi: 10.1038/ng921. Epub 2002 Jun 24.


Congenital cataracts cause 10-30% of all blindness in children, with one-third of cases estimated to have a genetic cause. Lamellar cataract is the most common type of infantile cataract. We carried out whole-genome linkage analysis of Chinese individuals with lamellar cataract, and found that the disorder is associated with inheritance of a 5.11-cM locus on chromosome 16. This locus coincides with one previously described for Marner cataract. We screened individuals of three Chinese families for mutations in HSF4 (a gene at this locus that encodes heat-shock transcription factor 4) and discovered that in each family, a distinct missense mutation, predicted to affect the DNA-binding domain of the protein, segregates with the disorder. We also discovered an association between a missense mutation and Marner cataract in an extensive Danish family. We suggest that HSF4 is critical to lens development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cataract / congenital
  • Cataract / genetics*
  • Child, Preschool
  • Chromosomes, Human, Pair 16
  • Conserved Sequence
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Linkage
  • Genome, Human
  • Heat Shock Transcription Factors
  • Humans
  • Infant
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation, Missense*
  • Pedigree
  • Sequence Homology, Amino Acid
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • HSF4 protein, human
  • Heat Shock Transcription Factors
  • Hsf4 protein, mouse
  • Transcription Factors