title: Pathogenic mutations in two families with congenital cataract identified with whole-exome sequencing.
abstract: OBJECTIVE
  Congenital cataract is one of the most frequent causes of visual impairment and childhood blindness. Approximately one quarter to one third of congenital cataract cases may have a genetic cause. However, phenotypic variability and genetic heterogeneity hamper correct genetic diagnosis. In this study, we used whole-exome sequencing (WES) to identify pathogenic mutations in two Korean families with congenital cataract.
  
  
  METHODS
  Two affected members from each family were pooled and processed for WES. The detected variants were confirmed with direct sequencing.
  
  
  RESULTS
  WES readily identified a CRYAA mutation in family A and a CRYGC mutation in family B. The c.61C>T (p.R21W) mutation in CRYAA has been previously reported in a family with congenital cataract and microcornea. The novel mutation, c.124delT, in CRYGC may lead to a premature stop codon (p.C42Afs*60).
  
  
  CONCLUSIONS
  This study clearly shows the efficacy of WES for rapid genetic diagnosis of congenital cataract with an unknown cause. WES will be the first choice for clinical services in the near future, providing useful information for genetic counseling and family planning.
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Yukiko
authors: Y
authors: Kondo
authors: Hirotomo
authors: H
authors: Saitsu
authors: Toshinobu
authors: T
authors: Miyamoto
authors: Byung Joo
authors: BJ
authors: Lee
authors: Kiyomi
authors: K
authors: Nishiyama
authors: Mitsuko
authors: M
authors: Nakashima
authors: Yoshinori
authors: Y
authors: Tsurusaki
authors: Hiroshi
authors: H
authors: Doi
authors: Noriko
authors: N
authors: Miyake
authors: Jeong Hun
authors: JH
authors: Kim
authors: Young Suk
authors: YS
authors: Yu
authors: Naomichi
authors: N
authors: Matsumoto
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D018389:Codon, Nonsense; D003459:Crystallins / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D016368:Frameshift Mutation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D056910:Republic of Korea; D017384:Sequence Deletion; D038222:gamma-Crystallins / Q000235:genetics*
chemical_list: C511246:CRYAA protein, human; D018389:Codon, Nonsense; C522806:Crygc protein, human; D003459:Crystallins; D038222:gamma-Crystallins