title: Mutation analysis in Chinese families with autosomal dominant hereditary cataracts.
abstract: OBJECTIVE
  To identify the molecular basis and clinical phenotype in three Chinese families with hereditary cataracts.
  
  
  METHODS
  Detailed family history and clinical data were recorded. The phenotypes were documented using slit-lamp photography. Candidate genes sequencing was performed to screen out the disease causing mutation. Bioinformatics analysis was performed to predict the function of mutant genes.
  
  
  RESULTS
  The phenotypes of the families were identified as nuclear cataract in Family 1, pulverulent cataract in Family 2, and nuclear cataract in Family 3. Direct sequencing revealed transversions of C > T at c.218 (p. S73F) in GJA8 in Family 1, A > C at c.125 (p. E42A) in GJA3 in Family 2, and C > T at c.268 (p. L90F) in GJA3 in Family 3. These mutations co-segregated with all affected individuals in the family and were not found in unaffected family members nor in the 100 unrelated controls. Bioinformatics analysis indicated that S73F in GJA8, E42A and L90F in GJA3 are highly conserved. S73F in GJA8, E42A and L90F in GJA3 could possibly be damaging predicted by PolyPhen-2, with score of 0.858, 1.000, 1.000, respectively.
  
  
  CONCLUSIONS
  This study identified three mutations in three Chinese families with hereditary cataracts. Of the three mutations, two were novel (c.125 A > C in GJA3 and c.268 C > T in GJA3), one was previously reported (c.218 C > T in GJA8).
authors.affiliation: a Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Eye Center , Beijing Tongren Hospital, Capital Medical University , Beijing , China .
authors.forename: Zhenfei
authors.initials: Z
authors.lastname: Yang
authors.affiliation: b Graduate School, Peking Union Medical College , Beijing , China .|c National Research Institute for Family Planning , Beijing , China and.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: b Graduate School, Peking Union Medical College , Beijing , China .|c National Research Institute for Family Planning , Beijing , China and.|d World Health Organization Collaborating Center for Research in Human Reproduction , Beijing , China.
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.affiliation: a Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Eye Center , Beijing Tongren Hospital, Capital Medical University , Beijing , China .
authors.forename: Si Quan
authors.initials: SQ
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002386:Cataract / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D000099264:Connexin 50
chemical_list: D017630:Connexins; D000099264:Connexin 50; C082917:GJA3 protein, human
keywords: E42A; GJA3; GJA8; L90F; S73F; hereditary cataract