title: A novel nonsense mutation in CRYGC is associated with autosomal dominant congenital nuclear cataracts and microcornea.
abstract: OBJECTIVE
  To report the identification of a novel nonsense mutation in CRYGC in a Chinese family with autosomal dominant congenital nuclear cataracts and microcornea.
  
  
  METHODS
  We investigated a four-generation Chinese family with six members affected with nuclear cataracts and microcornea. The family resides in a relatively isolated region of northern China. Genomic DNA was isolated from blood leucocytes, genotyping was performed using more than 100 microsatellite markers for the known cataract candidate gene loci, and LOD scores were calculated using the LINKAGE programs. Mutations were detected by DNA sequence analysis of the candidate genes.
  
  
  RESULTS
  Evidence for linkage was detected at marker D2S325 (LOD score [Z]=2.29, recombination fraction [theta]=0.0), which closely flanks the gamma-crystallin gene cluster (CRYGA-CRYGD) on chromosome 2q32.3-q35. Direct sequencing of the candidate CRYGA-CRYGD gene cluster revealed a c.470G>A transversion in exon 3 of CRYGC, which cosegregated with cataracts in the family and was not observed in 100 normal controls. This single nucleotide change was predicted to introduce a translation stop codon at tryptophan 157 (W157X).
  
  
  CONCLUSIONS
  The present study has identified a novel nonsense mutation in CRYGC associated with autosomal dominant cataracts and microcornea in a Chinese family. Our finding expands the spectrum of CRYGC mutations associated with congenital cataract and confirms the role of gamma-crystallin in the pathogenesis of congenital nuclear cataracts.
authors.affiliation: Eye hospital, the First Affiliated Hospital, Harbin Medical University, Harbin, China. hljzhanglu@gmail.com
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Songbin
authors.initials: S
authors.lastname: Fu
authors.forename: Yangshan
authors.initials: Y
authors.lastname: Ou
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Su
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002681:China; D018389:Codon, Nonsense; D003315:Cornea / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D038222:gamma-Crystallins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C522806:Crygc protein, human; D038222:gamma-Crystallins