Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans

J Med Genet. 2005 Sep;42(9):706-10. doi: 10.1136/jmg.2004.028274.


Background: Congenital or childhood cataract is clinically and genetically a highly heterogeneous lens disorder in children. Autosomal dominant inheritance is most common.

Objective: To report the identification of a mutation in the human CRYGS gene.

Subjects and methods: A large six generation family affected by progressive polymorphic cortical cataract was investigated. After excluding loci for known cataract candidate genes using 39 fluorescent microsatellite markers, a whole genome scan was carried out.

Results: The disease was associated with inheritance of a 20.7 cM locus on chromosome 3q26.3-qter, with a maximum LOD score of 6.34 (theta = 0) at marker D3S1602. Haplotype analysis indicated that the disease gene lay at approximately 2.8 Mb physical intervals between D3S1571 and D3S3570 and contained CRYGS on 3q27.3. By sequencing the CRYGS gene, a distinct 1619G-->T (AC068631) heterozygous missense mutation in exon 2 was identified, co-segregating with the disease phenotype in this family and resulting in a glycine (GGC) to valine residue (GTC) substitution in codon 18 (NP_060011).

Conclusions: This report is the first description of a mutation in CRYGS with autosomal dominant cataract in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cataract / congenital
  • Cataract / genetics*
  • China
  • DNA Mutational Analysis
  • Family
  • Genes, Dominant*
  • Haplotypes
  • Humans
  • Lod Score
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Sequence Alignment
  • gamma-Crystallins / genetics*


  • gamma-Crystallins
  • CRYGS protein, human

Associated data

  • GENBANK/AC068631
  • OMIM/121015
  • OMIM/123580
  • OMIM/123590
  • OMIM/123610
  • OMIM/123620
  • OMIM/123680
  • OMIM/123690
  • OMIM/154045
  • OMIM/154050
  • OMIM/600429
  • OMIM/600897
  • OMIM/600929
  • OMIM/602438
  • OMIM/603212
  • RefSeq/NP_060011