title: Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts.
abstract: OBJECTIVE
  We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital coralliform cataracts and demonstrate the functional analysis of a candidate gene in the family.
  
  
  METHODS
  Family history data were recorded. Clinical and ophthalmologic examinations were performed on affected and unaffected family members. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point LOD scores were calculated using the Linkage software after genotyping. A mutation was detected by direct sequencing, using gene-specific primers. Wild-type and mutant proteins were analyzed with online software.
  
  
  RESULTS
  Affected members of this family had coralliform cataracts. Linkage analysis was obtained at markers, D2S72 (LOD score [Z]=3.31, recombination fraction [theta]=0.0) and D2S1782 (Z=3.01, theta=0.0). Haplotype analysis indicated that the cataract gene was closely linked to these two markers. Sequencing the gammaD-crystallin gene (CRYGD) revealed a G>T transversion in exon 2, which caused a conservative substitution of Gly to Cys at codon 61 (P.G61C). This mutation co-segregated with the disease phenotype in all affected individuals and was not observed in any of the unaffected or 100 normal, unrelated individuals. Bioinformatic analyses showed that a highly conserved region was located around Gly61. Data generated with online software revealed that the mutation altered the protein's stability, solvent-accessibility, and interactions with other proteins.
  
  
  CONCLUSIONS
  This is the first reported case of a congenital coralliform cataract phenotype associated with the mutation of Gly61Cys (P.G61C) in the CRYGD gene; it demonstrates a possible mechanism of action for the mutant gene.
authors.affiliation: Graduate School, Peking Union Medical College, Beijing, China.
authors.forename: Feifeng
authors.initials: F
authors.lastname: Li
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Gao
authors.forename: Shiguo
authors.initials: S
authors.lastname: Liu
authors.forename: Baojian
authors.initials: B
authors.lastname: Zhao
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Shangzhi
authors.initials: S
authors.lastname: Huang
authors.forename: Siquan
authors.initials: S
authors.lastname: Zhu
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D002877:Chromosomes, Human / Q000235:genetics; D003459:Crystallins / Q000737:chemistry / Q000235:genetics*; D003545:Cysteine / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D005819:Genetic Markers; D005998:Glycine / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007908:Lens, Crystalline / Q000473:pathology; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009691:Nucleic Acid Denaturation; D010375:Pedigree; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D038222:gamma-Crystallins
chemical_list: C504903:CRYGD protein, human; D003459:Crystallins; D005819:Genetic Markers; D020033:Protein Isoforms; D038222:gamma-Crystallins; D003545:Cysteine; D005998:Glycine