title: Autosomal-dominant cerulean cataract in a chinese family associated with gene conversion mutation in beta-B2-crystallin.
abstract: OBJECTIVE
  Our purpose was to identify the genetic defect in a Chinese cerulean cataract family.
  
  
  METHODS
  After obtaining informed consent, genomic DNA was extracted from leukocytes. Genotyping and 2-point linkage analysis were carried out using the MLINK component of the LINKAGE program package version 5.10. Mutational analysis of the candidate gene was performed by bidirectional sequencing. The structure homology modeling of the mutant protein was based on Swiss-Model Serve, and its structure was displayed and compared with native beta-B2-crystallin using the RasMol software.
  
  
  RESULTS
  The disease locus was mapped within a 4.05-cM interval on 22q11.22-22q12.1. By sequencing, a cytosine to thymine transition (NM_000496.2:c.463C>T) was detected in exon 6 of CRYBB2, which resulted in the insertion of a premature stop codon (p.Q155X). In addition, there existed another transition (NM_000496.2:c.471C>T) in the same exon, which does not change the amino acid sequence. Neither NM_000496.2:c.463C>T nor NM_000496.2:c.471C>T were found in 171 normal Chinese controls. The homology modeling showed that the second structure of the mutant protein was different from that of native human beta-B2-crystallin.
  
  
  CONCLUSIONS
  This is the first report of congenital cerulean cataract associated with a mutation in CRYBB2 in a Chinese family. This finding further strengthens the association between CRYBB2 and cerulean cataracts. Two transitions, NM_000496.2:c.463C>T and NM_000496.2:c.471C>T, in CRYBB2 are identical to the sequence of CRYBB2P1, which has over 97% homology to CRYBB2. This supports the possibility of gene conversion between CRYBB2 and CRYBB2P1 as a mechanism responsible for congenital cataract.
authors.affiliation: Department of Ophthalmology, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Lin
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Gu
authors.forename: Hong
authors.initials: H
authors.lastname: Su
authors.forename: Shangzhi
authors.initials: S
authors.lastname: Huang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Qi