title: A missense mutation in the gammaD-crystallin gene CRYGD associated with autosomal dominant congenital cataract in a Chinese family.
abstract: OBJECTIVE
  To identify the genetic defect in autosomal dominant congenital cataracts in a six generation Chinese family.
  
  
  METHODS
  Clinical and ophthalmological examinations were performed on the affected and unaffected family members. All the members were genotyped with microsatellite markers at loci which were considered to be associated with cataracts. A two-point LOD score was calculated using the Linkage package after genotyping. A mutation was detected by direct sequencing using gene specific primers.
  
  
  RESULTS
  Clinical heterogeneity was observed within this family, three affected individuals showed nuclear cataract and others had coralliform cataracts. Significant evidence of linkage was obtained at markers D2S325 (LOD score [Z]=3.10, recombination fraction [theta]=0.0) and D2S1782 (Z=5.97, theta=0.0), respectively. Haplotype analysis indicated that the cataract gene was close to those two markers. Sequencing of the gammaD-crystallin gene (CRYGD) revealed a C>T transition in exon 2, that causes a conservative substitution of Arg to Cys at codon 14 (R14C). This mutation co-segregated with all affected individuals and was not observed in unaffected or 100 normal unrelated individuals. Bioinformatic analyses also showed that a highly conserved region was located at Arg14.
  
  
  CONCLUSIONS
  This study is the first reported case with phenotype of coralliform/nuclear cataract that associated with the mutation of Arg14Cys (R14C) CRYGD.
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Beijing, China. gufengpumc@yahoo.com.cn
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Xi Xin
authors.initials: XX
authors.lastname: Ma
authors.forename: Li Song
authors.initials: LS
authors.lastname: Shi
authors.forename: Shang Zhi
authors.initials: SZ
authors.lastname: Huang
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002386:Cataract / Q000150:complications / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D003459:Crystallins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D016415:Sequence Alignment; D038222:gamma-Crystallins
chemical_list: C504903:CRYGD protein, human; D003459:Crystallins; D038222:gamma-Crystallins