title: A Novel Insertion Variant of CRYGD Is Associated with Congenital Nuclear Cataract in a Chinese Family.
abstract: OBJECTIVE
  To investigate a novel insertion variant of CRYGD identified in a Chinese family with nuclear congenital cataract.
  
  
  METHODS
  A Chinese family with congenital nuclear cataract was recruited for the mutational screening of candidate genes by direct sequencing. Recombinant N-terminal Myc tagged wildtype or mutant CRYGD was expressed in HEK293T cells. The expression pattern, protein solubility and subcellular distribution were analyzed by western blotting and immunofluorescence.
  
  
  RESULTS
  A novel insertion variant, c.451_452insGACT, in CRYGD was identified in the patients. It causes a frameshift and a premature termination of the polypeptide to become Y151*. A significantly reduced solubility was observed for this mutant. Unlike wildtype CRYGD, which existed mainly in the cytoplasm, Y151* was mis-located in the nucleus.
  
  
  CONCLUSIONS
  We have identified a novel mutation, c.451_452insGACT, in CRYGD, which is associated with nuclear cataract. This is the first insertion mutation of CRYGD found to cause autosomal dominant congenital cataract. The mutant protein, with loss of solubility and localization to the nucleus, is hypothesized to be the major cause of cataract in these patients.
authors.affiliation: Department of Ophthalmology, Shengjing Hospital, China Medical University, Shenyang, China; Department of Ophthalmology, The Fourth People's Hospital of Shenyang, Shenyang, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China; Central Laboratory, Central Hospital of Zibo, Zibo, China.
authors.forename: Lianqing
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Zixun
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Ophthalmology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
mesh_terms: D044466:Asian People / Q000235:genetics; D002386:Cataract / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D010375:Pedigree; D038222:gamma-Crystallins / Q000235:genetics*
chemical_list: C504903:CRYGD protein, human; D038222:gamma-Crystallins