title: Exome sequencing identifies a novel mutation in GJA8 associated with inherited cataract in a Chinese family.
abstract: BACKGROUND
  Congenital cataract is a clinical and genetic heterogeneous group of eye disorders that causes visual impairment and childhood blindness. In this study, a Chinese family with congenital cataract is studied.
  
  
  METHODS
  In order to identify the genetic defects which were associated with congenital cataract, a whole-exome sequencing approach is performed to screen for the potential mutation-causing disease.
  
  
  RESULTS
  The result revealed a novel heterozygous mutation (c.433G > T; p.G145W) in exon 2 the of GJA8 gene, which can be detected in all affected individuals, but not the unaffected family members. Meanwhile, this novel mutation cannot be retrieved in 100 healthy local Chinese controls and five other SNPs databases (dbSNP, ESP, ExAC, HTD and HGVD). Moreover, p.G145W was predicted as a mutation with pathogenicity by using bioinformatics methods, including PolyPhen-2, SIFT, PROVEAN, SNPs3D and the mutation significance cutoff (MSC). However, molecular function analysis of this novel mutation (p.G145W, GJA8) indicated that it did not affect the subcellular distributions and the trafficking of GJA8 protein to the plasma membrane. The truth of pathogenic significance with this novel mutation in GJA8 gene needed to be further studied.
  
  
  CONCLUSIONS
  The c.433G > T (p.G145W) mutation in the GJA8 gene was first reported to our best knowledge. The results of our study would further broaden the mutation spectrum of GJA8 associated with congenital cataract.
authors: Department of Ophthalmology, Xi'an fourth hospital, Xi'an, Shaanxi Province, People's Republic of China.
authors: Mei
authors: M
authors: Ren
authors: Department of Ophthalmology, Xi'an fourth hospital, Xi'an, Shaanxi Province, People's Republic of China. yangxinguang62@Hotmail.com.
authors: Xin Guang
authors: XG
authors: Yang
authors: Department of Ophthalmology, Xi'an fourth hospital, Xi'an, Shaanxi Province, People's Republic of China.
authors: Xiao Jie
authors: XJ
authors: Dang
authors: Department of Ophthalmology, Xi'an fourth hospital, Xi'an, Shaanxi Province, People's Republic of China.
authors: Jin An
authors: JA
authors: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D002386:Cataract / Q000151:congenital / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D055815:Young Adult; D000099264:Connexin 50
chemical_list: D017630:Connexins; D004247:DNA; D008562:Membrane Glycoproteins; D000099264:Connexin 50
keywords: Autosomal dominant; Congenital cataract; Exome-sequencing; GJA8