title: A novel mutation in GJA3 associated with congenital Coppock-like cataract in a large Chinese family.
abstract: OBJECTIVE
  To identify the potential pathogenic mutation over five generations of a Chinese family with congenital Coppock-like cataracts (CCL).
  
  
  METHODS
  We investigated five generations of a Chinese family affected with CCL. The family resides in a relatively isolated region of northern China. Peripheral blood samples were collected from all of the family members, and genomic DNA was then extracted from the blood samples. A genome-wide linkage scan was performed using about 400 microsatellite markers. Two-point LOD (linkage odd disequilibrium) scores (Z) were calculated using the LINKAGE programs (ver. 5.1). Cyrillic software processed the resulting haplotypes. Mutation detection was performed in the candidate gene by direct sequencing.
  
  
  RESULTS
  The maximum LOD score was obtained at marker D13S175 (lod score [Z(max)]=5.90; recombination fraction [θ]=0.0). Haplotype analysis traced the disease gene to a 6.99-cM interval bounded by D13S1316 and D13S1275 on chromosome 13q12.11. Direct sequencing of the candidate gene GJA3 (gap junction protein alpha-3) revealed a c.427G>A transition in exon 2 of GJA3 that co-segregated with the cataract in the family members and was not observed in 100 control patients. This single-nucleotide change resulted in the substitution of a highly conserved glycine by arginine (G143R).
  
  
  CONCLUSIONS
  The present study identified a novel mutation in GJA3 that causes CCL. As the first report to relate p.G143R mutation in GJA3, it expands the mutation spectrum of GJA3. Our report is the first in identification of the mutation of GJA3 in the cytoplasmic-loop domain. This mutation is associated with multiple members of a five-generation family with congenital CCL.
authors.affiliation: Eye Hospital, the First Affiliated Hospital, Harbin Medical University, Harbin, China. 13796089809@163.com
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Qu
authors.forename: Sheng
authors.initials: S
authors.lastname: Su
authors.forename: Linan
authors.initials: L
authors.lastname: Guan
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002648:Child; D002882:Chromosomes, Human, Pair 13; D017630:Connexins / Q000235:genetics*; D005091:Exons; D005190:Family; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D017630:Connexins; C082917:GJA3 protein, human