title: Another evidence for a D47N mutation in GJA8 associated with autosomal dominant congenital cataract.
abstract: OBJECTIVE
  To identify the pathogenic gene mutation in a Chinese family with autosomal dominant inherited nuclear cataract.
  
  
  METHODS
  After obtained informed consent, detailed ophthalmic examinations were performed, genomic DNAs were obtained from eighteen family members in a four-generation Chinese family with five affected. All exons of candidate genes were amplified by polymerase chain reaction (PCR) and were sequenced performed by bidirectional sequencing. The stability of mutation was predicted with Prediction of Protein Mutant Stability changes (PoPMuSiC). The structure homology modeling of the mutant protein was based on Swiss-Model Serve, and its structure was displayed and compared with human connexin26 using the RasMol software.
  
  
  RESULTS
  By sequencing the encoding regions of the candidate genes, a missence mutation (c.139G>A) was detected in gap junction protein alpha 8 (GJA8) gene, which resulted in the substitution of highly conserved aspartic acid by asparagine at codon 47 (p.D47N). The mutation co-segregated with all patients and was absent in 100 normal Chinese controls. PoPMuSiC analysis showed the change in folding free energy upon mutation (ΔΔG) is 0.31 kcal/mol and the mutation p.D47N is destabilizing. The homology modeling showed that the structure of the mutant protein was different with that of human connexin26.
  
  
  CONCLUSIONS
  The study identified a missence mutation (c.139G>A) in GJA8 gene associated with autosomal dominant congenital cataract in a Chinese family. It gave further evidence for GJA8 associated 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: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Wen
authors.initials: W
authors.lastname: Wen
authors.forename: Shenghai
authors.initials: S
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
mesh_terms: D044466:Asian People / Q000235:genetics*; D001216:Asparagine / Q000235:genetics / Q000378:metabolism*; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002386:Cataract / Q000151:congenital / Q000235:genetics* / Q000378:metabolism; D000072259:Connexin 26; D017630:Connexins / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013816:Thermodynamics; D000099264:Connexin 50
chemical_list: D001216:Asparagine; D001224:Aspartic Acid; D000072259:Connexin 26; D017630:Connexins; D005136:Eye Proteins; D050505:Mutant Proteins; D000099264:Connexin 50; C000607042:GJB2 protein, human