title: Congenital anterior polar cataract associated with a missense mutation in the human alpha crystallin gene CRYAA.
abstract: OBJECTIVE
  To identify the potential pathogenic mutation over four generations of a Chinese family with congenital anterior polar cataracts (APC).
  
  
  METHODS
  We investigated four generations of a Chinese family who are afflicted with anterior polar cataracts. 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 gene scan was performed using about 400 primers labeled with fluorescent stain. Linkage software defined the region of the diseased gene with a Linkage analysis, and Cyrillic software processed the resulting haplotypes. Mutation detection was performed in the candidate gene by sequencing amplified products.
  
  
  RESULTS
  A maximum logarithm of odds score (LOD) score was obtained at marker D21S1252(LOD score [Z]=3.23, recombination fraction [θ]=0.0. Haplotype analysis traced the disease gene to an 18.47 cM region bounded by D21S263 and D21S266 on chromosome21q22.11-q22.3. Direct sequencing of the candidate alpha A crystallin (CRYAA) gene revealed a c.347G>A transition in exon 3 of CRYAA 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 Arginine by Histidine (R116H).
  
  
  CONCLUSIONS
  The present study identified a missense mutation (R116H) in the CRYAA gene that causes autosomal dominant congenital anterior polar cataracts in a Chinese family. Our finding confirms the high rate of apparently independent mutations at this dinucleotide.
authors: Eye Hospital, the First Affiliated Hospital, Harbin Medical University, Harbin, China. hljzhanglu@gmail.com
authors: Lu
authors: L
authors: Zhang
authors: Yi
authors: Y
authors: Zhang
authors: Ping
authors: P
authors: Liu
authors: Wenping
authors: W
authors: Cao
authors: Xianling
authors: X
authors: Tang
authors: Sheng
authors: S
authors: Su
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002386:Cataract / Q000151:congenital* / Q000235:genetics; D002891:Chromosomes, Human, Pair 21; D003459:Crystallins / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis; D005799:Genes, Dominant; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: C511246:CRYAA protein, human; D003459:Crystallins; D017931:DNA Primers; D005456:Fluorescent Dyes