title: A novel GJA8 mutation (p.I31T) causing autosomal dominant congenital cataract in a Chinese family.
abstract: OBJECTIVE
  To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family.
  
  
  METHODS
  Family history and clinical data were recorded. The genomic DNA was extracted from peripheral blood leukocytes. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point logarithm of odds (LOD) scores were calculated by using the Linkage software after genotyping. Mutations were detected by DNA sequence analysis of the candidate genes. Effects of amino acid changes on the structure and function of proteins were predicted by bioinformatics analysis.
  
  
  RESULTS
  Evidence of a linkage was obtained at markers D1S514 (LOD score [Z]=3.48, recombination fraction [theta]=0.0) and D1S1595 (Z=2.49, theta=0.0). Haplotype analysis indicated that the cataract gene was close to these two markers. Sequencing of the connexin 50 (GJA8) gene revealed a T>C transition at nucleotide position c.92. This nucleotide change resulted in the substitution of highly conserved isoleucine by threonine at codon 31(I31T). This mutation co-segregated with all affected individuals and was not observed in unaffected or 110 normal unrelated individuals. Bioinformatics analysis showed that a highly conserved region was located at Ile31, and the mutation was predicted to affect the function and secondary structure of the GJA8 protein.
  
  
  CONCLUSIONS
  A novel mutation in GJA8 was detected in a Chinese family with autosomal dominant congenital nuclear cataract, providing clear evidence of a relationship between the genotype and the corresponding cataract phenotype.
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Kaijie
authors.initials: K
authors.lastname: Wang
authors.forename: Binbin
authors.initials: B
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Shiyi
authors.initials: S
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Yun
authors.forename: Peisu
authors.initials: P
authors.lastname: Suo
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.forename: Siquan
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D017630:Connexins / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005190:Family; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D008040:Genetic Linkage; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017433:Protein Structure, Secondary; D055815:Young Adult; D000099264:Connexin 50
chemical_list: D017630:Connexins; D005136:Eye Proteins; D050505:Mutant Proteins; D000099264:Connexin 50