title: A novel mutation in γD-crystallin associated with autosomal dominant congenital cataract in a Chinese family.
abstract: OBJECTIVE
  To identify the pathogenic gene mutation in a Chinese family with autosomal dominant congenital nuclear cataract.
  
  
  METHODS
  After obtaining informed consent, detailed ophthalmic examinations were performed and genomic DNAs were obtained from eleven family members in a three-generation Chinese family with five affected. All exons of candidate genes associated with congenital nuclear cataract were amplified by polymerase chain reaction (PCR) and the PCR products were sequenced in both directions. The hydrophobic property of the mutant protein was analyzed with bioinformatics program ProtScale. The structure homology modeling of the mutant protein was based on Swiss-Model Serve, and its structure was displayed and compared with native γD-crystallin (CRYGD) using the RasMol software.
  
  
  RESULTS
  By sequencing the encoding regions of the candidate genes, a novel mutation (c.110G>C) was detected in exon 2 of CRYGD, which resulted in the substitution of a highly conserved arginine by proline at codon 36 (p.R36P). The mutation co-segregated with all patients and was absent in 100 normal Chinese controls. Bioinformatics analysis showed an obvious increase of the local hydrophilicity of the R36P mutant γD-crystallin. The homology modeling showed that the structure of the mutant protein was similar with that of native human γD-crystallin.
  
  
  CONCLUSIONS
  The study identified a novel mutation (c. 110G>C) in CRYGD associated with autosomal dominant congenital cataract in a Chinese family. It expands the mutation spectrum of CRYGD in association with congenital cataract.
authors.affiliation: Department of Ophthalmology, Eye and ENT hospital of Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Xueli
authors.initials: X
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Jihong
authors.initials: J
authors.lastname: Wu
authors.forename: Boqi
authors.initials: B
authors.lastname: Yang
authors.forename: Xinghuai
authors.initials: X
authors.lastname: Sun
mesh_terms: D001120:Arginine / Q000235:genetics / Q000378:metabolism*; D044466:Asian People / Q000235:genetics; D002386:Cataract / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008958:Models, Molecular; D050505:Mutant Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011392:Proline / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D038222:gamma-Crystallins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C504903:CRYGD protein, human; D050505:Mutant Proteins; D038222:gamma-Crystallins; D001120:Arginine; D011392:Proline