title: Exome Sequencing and Epigenetic Analysis of Twins Who Are Discordant for Congenital Cataract.
abstract: OBJECTIVE
  To further understand genetic factors that contribute to congenital cataracts, we sought to identify early post-twinning mutational and epigenetic events that may account for the discordant phenotypes of a twin pair.
  
  
  METHODS
  A patient with a congenital cataract and her twin sister were assessed for genetic factors that might contribute to their discordant phenotypes by mutation screening of 11 candidate genes (CRYGC, CRYGD, CRYAA, CRYAB, CRYBA1, CRYBB1, CRYBB2, MIP, HSF4, GJA3, and GJA8), exome analysis followed by Sanger sequencing of 10 additional candidate genes (PLEKHO2, FRYL, RBP3, P2RX2, GSR, TRAM1, VEGFA, NARS2, CADPS, and TEKT4), and promoter methylation analysis of five representative genes (TRAM1, CRYAA, HSF4, VEGFA, GJA3, DCT) plus one additional candidate gene (FTL).
  
  
  RESULTS
  Mutation screening revealed no gene mutation differences between the patient and her twin sister for the 11 candidate genes. Exome sequencing analysis revealed variations between the twins in 442 genes, 10 of which are expressed in the eye. However, these differential variants could not be confirmed by Sanger sequencing. Furthermore, epigenetic discordance was not detected in the twin pair.
  
  
  CONCLUSIONS
  The genomic DNA mutational and epigenetic events assessed in this study could not explain the discordance in the development of phenotypic differences between the twin pair, suggesting the possible involvement of somatic mutations or environmental factors. Identification of possible causes requires further research.
authors.affiliation: Department of Ophthalmology,Center for Gene Diagnosis,Zhongnan Hospital,Wuhan University,Wuhan,China.
authors.forename: Tanwei
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Ophthalmology,Center for Gene Diagnosis,Zhongnan Hospital,Wuhan University,Wuhan,China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Third Affiliated Hospital of Sun Yat-sen University,Guanzhou,Guandong,China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology,Center for Gene Diagnosis,Zhongnan Hospital,Wuhan University,Wuhan,China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology,Center for Gene Diagnosis,Zhongnan Hospital,Wuhan University,Wuhan,China.
authors.forename: Chen
authors.initials: C
authors.lastname: Qiao
authors.affiliation: Department of Ophthalmology,Center for Gene Diagnosis,Zhongnan Hospital,Wuhan University,Wuhan,China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
mesh_terms: D002386:Cataract / Q000151:congenital / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D019175:DNA Methylation / Q000235:genetics; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D010375:Pedigree; D014430:Twins, Monozygotic / Q000235:genetics
keywords: MSRE-PCR; congenital cataract; exome sequencing; methylation sensitive restriction enzyme-polymerase chain reaction; twins