A family with autosomal dominant primary congenital cataract associated with a CRYGC mutation: evidence of clinical heterogeneity

Mol Vis. 2007 Jul 26:13:1333-8.

Abstract

Purpose: To describe a family with primary congenital cataract associated with a CRYGC mutation.

Methods: One family with several affected members with primary congenital cataract and 170 healthy controls were examined. DNA from leukocytes was isolated to analyze the CRYGA-D gene cluster.

Results: DNA sequencing analysis of the CRYGA-D gene cluster of the affected members showed the heterozygous missense mutation c.502C>T in the CRYGC gene. This transition mutation resulted in the substitution of Arg at position 168 by Trp. Analysis of the healthy members of the family and 170 unrelated controls showed a normal sequence of the CRYGA-D gene cluster.

Conclusions: In the present study, we described a family with nuclear congenital cataract that segregated the CRYGC missense mutation c.502C>T. This mutation has been associated with the phenotype of lamellar cataract but is also considered a single nucleotide polymorphism (SNP) in the NCBI database. Our data and previous report support that R168W is the actual disease-causing mutation and should no longer be considered a SNP. This is the first case of phenotypic heterogeneity in the primary congenital cataract specifically associated with the R168W mutation in the CRYGC gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cataract / genetics*
  • Codon / genetics
  • DNA Mutational Analysis
  • Exons / genetics
  • Female
  • Genes, Dominant*
  • Genetic Heterogeneity*
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Sequence Alignment
  • gamma-Crystallins / chemistry
  • gamma-Crystallins / genetics*

Substances

  • Codon
  • Crygc protein, human
  • gamma-Crystallins