title: A novel gammaD-crystallin mutation causes mild changes in protein properties but leads to congenital coralliform cataract.
abstract: OBJECTIVE
  To identify the genetic lesions for congenital coralliform cataract.
  
  
  METHODS
  Two Chinese families with autosomal dominant coralliform cataract, 12 affected and 14 unaffected individuals, were recruited. Fifteen known genes associated with autosomal dominant congenital cataract were screened by two-point linkage analysis with gene based single nucleotide polymorphisms and microsatellite markers. Sequence variations were identified. Recombinant FLAG-tagged wild type or mutant gammaD-crystallin was expressed in human lens epithelial cells and COS-7 cells. Protein solubility and intracellular distribution were analyzed by western blotting and immunofluorescence, respectively.
  
  
  RESULTS
  A novel heterozygous change, c.43C>A (R15S) of gammaD-crystallin (CRYGD) co-segregated with coralliform cataract in one family and a known substitution, c.70C>A (P24T), in the other family. Unaffected family members and 103 unrelated control subjects did not carry these mutations. Similar to the wild type protein, R15S gammaD-crystallin was detergent soluble and was located in the cytoplasm. ProtScale and ScanProsite analyses revealed raised local hydrophobicity and the creation of a hypothetical casein kinase II phosphorylation site.
  
  
  CONCLUSIONS
  A novel R15S mutation caused congenital coralliform cataract in a Chinese family. R15S possessed similar properties to the wild type gammaD-crystallin, but its predicted increase of hydrophobicity and putative phosphorylation site could lead to protein aggregation, subsequently causing opacification in lens.
authors: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors: Li-Yun
authors: LY
authors: Zhang
authors: Bo
authors: B
authors: Gong
authors: Jian-Ping
authors: JP
authors: Tong
authors: Dorothy Shu-Ping
authors: DS
authors: Fan
authors: Sylvia Wai-Yee
authors: SW
authors: Chiang
authors: Dinghua
authors: D
authors: Lou
authors: Dennis Shun-Chiu
authors: DS
authors: Lam
authors: Gary Hin-Fai
authors: GH
authors: Yam
authors: Chi-Pui
authors: CP
authors: Pang
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics; D044466:Asian People; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009928:Organ Specificity; D010375:Pedigree; D021381:Protein Transport; D012694:Serine / Q000235:genetics; D012995:Solubility; D038222:gamma-Crystallins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: C504903:CRYGD protein, human; D050505:Mutant Proteins; D038222:gamma-Crystallins; D012694:Serine; D001120:Arginine