CRYBB1 mutation associated with congenital cataract and microcornea

Mol Vis. 2005 Aug 8;11:587-93.

Abstract

Purpose: The molecular characterization of a UK family with an autosomal dominant congenital cataract associated with microcornea is reported.

Methods: Family history and clinical data were recorded. This phenotype was linked to a 7.6 cM region of chromosome 22q11.2-q12.2, spanning the beta-crystallin gene cluster (ZMax of 3.91 for marker D22S1114 at theta=0). Candidate genes were PCR amplified and screened for mutations on both strands using direct sequencing.

Results: Sequencing of the coding regions and flanking intronic sequences of CRYBB2 and CRYBB1 showed the presence of a novel, heterozygous X253R change in exon 6 of CRYBB1. SSCP analysis confirmed that this sequence change segregated with the disease phenotype in all available family members and was not found in 109 ethnically matched controls.

Conclusions: X253R is predicted to elongate the COOH-terminal extension of the protein and would be expected to disrupt beta-crystallin interactions. This is the first documented involvement of CRYBB1 in ocular development beyond cataractogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cataract / congenital*
  • Child
  • Chromosomes, Human, Pair 22 / genetics*
  • Cornea / abnormalities*
  • DNA Mutational Analysis
  • Eye Abnormalities / genetics*
  • Female
  • Genes, Dominant
  • Genetic Linkage
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • beta-Crystallin B Chain / genetics*

Substances

  • CRYBB1 protein, human
  • beta-Crystallin B Chain