title: A novel nonsense mutation in CRYBB1 associated with autosomal dominant congenital cataract.
abstract: OBJECTIVE
  To identify the molecular defect underlying an autosomal dominant congenital nuclear cataract in a Chinese family.
  
  
  METHODS
  Twenty-two members of a three-generation pedigree were recruited, clinical examinations were performed, and genomic DNA was extracted from peripheral blood leukocytes. All members were genotyped with polymorphic microsatellite markers adjacent to each of the known cataract-related genes. Linkage analysis was performed after genotyping. Candidate genes were screened for mutation using direct sequencing. Individuals were screened for presence of a mutation by restriction fragment length polymorphism (RFLP) analysis.
  
  
  RESULTS
  Linkage analysis identified a maximum LOD score of 3.31 (recombination fraction [theta]=0.0) with marker D22S1167 on chromosome 22, which flanks the beta-crystallin gene cluster (CRYBB3, CRYBB2, CRYBB1, and CRYBA4). Sequencing the coding regions and the flanking intronic sequences of these four candidate genes identified a novel, heterozygous C-->T transition in exon 6 of CRYBB1 in the affected individuals of the family. This single nucleotide change introduced a novel BfaI site and was predicted to result in a nonsense mutation at codon 223 that changed a phylogenetically conserved amino acid to a stop codon (p.Q223X). RFLP analysis confirmed that this mutation co-segregated with the disease phenotype in all available family members and was not found in 100 normal unrelated individuals from the same ethnic background.
  
  
  CONCLUSIONS
  This study has identified a novel nonsense mutation in CRYBB1 (p.Q223X) associated with autosomal dominant congenital nuclear cataract.
authors.affiliation: Biomedical Engineering Center of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Juhua
authors.initials: J
authors.lastname: Yang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhu
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Xiang
authors.initials: X
authors.lastname: He
authors.forename: Zongfu
authors.initials: Z
authors.lastname: Cao
authors.forename: Xuexi
authors.initials: X
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Tong
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D038206:beta-Crystallin B Chain / Q000737:chemistry / Q000235:genetics*
chemical_list: C105601:CRYBB1 protein, human; D018389:Codon, Nonsense; D038206:beta-Crystallin B Chain