title: Association of ZEB1 and TCF4 rs613872 changes with late onset Fuchs endothelial corneal dystrophy in patients from northern India.
abstract: OBJECTIVE
  Fuchs endothelial corneal dystrophy (FECD) results in loss of vision associated with progressive corneal edema and loss of corneal transparency. The aim of the study was to evaluate changes in ZEB1, COL8A2, SLC4A11, and TCF4 rs613872 and correlate them with clinical findings.
  
  
  METHODS
  Eighty-two patients with clinically diagnosed FECD and 143 controls were recruited during the period 2007-2012. Clinical details, pedigree information up to three generations, and 5 ml of blood samples were collected. Histopathological and transmission electron microscopy studies were performed on host corneal buttons from patients who underwent keratoplasty. Genomic DNA from blood was processed for PCR amplification followed by direct sequencing to screen genetic changes in the candidate genes. The pathogenic nature of the genetic variants was assessed using Sorting Intolerant From Tolerant (SIFT) and MutationTaster.
  
  
  RESULTS
  The mean age at the onset of symptoms was 59.14±1.41years, the male to female ratio was 1:1.5, and the mean specular count (endothelial cell density) was 1629±93.62 cells/mm(2) with a mean central corneal thickness (CCT) of 617.30±15.73 µm. ZEB1 showed a novel variant IVS2+276 C/T in 14% of the cases, a novel nonsense p.Leu947stop mutation in one patient, two novel missense mutations (p.Glu733Lys, p.Ala818Val) in one patient each, and one novel synonymous variation (p.Ser234Ser) in two patients. Reported mutation p.Gln840Pro and five polymorphisms were also identified. The TCF4 single nucleotide polymorphism (SNP) rs613872 was significantly higher in patients with FECD.
  
  
  CONCLUSIONS
  This is the first report of genetic variations in ZEB1 and TCF4 SNP rs613872 in patients with FECD from northern India that suggests a possible role in disease pathogenesis and the regulation of endothelial cell density.
authors.affiliation: Department of Anatomy, AIIMS, New Delhi, India.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India.
authors.forename: Babu Lal
authors.initials: BL
authors.lastname: Kumawat
authors.affiliation: Department of Anatomy, AIIMS, New Delhi, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Paliwal
authors.affiliation: Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India.
authors.forename: Radhika
authors.initials: R
authors.lastname: Tandon
authors.affiliation: Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India.
authors.forename: Namrata
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India.
authors.forename: Seema
authors.initials: S
authors.lastname: Sen
authors.affiliation: Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India.
authors.forename: Seema
authors.initials: S
authors.lastname: Kashyap
authors.affiliation: Department of Anatomy, AIIMS, New Delhi, India.
authors.forename: Tapas Chandra
authors.initials: TC
authors.lastname: Nag
authors.affiliation: Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India ; Center for Eye Research, Australia, Northwest Academic Centre, University of Melbourne, Australia.
authors.forename: Rasik B
authors.initials: RB
authors.lastname: Vajpayee
authors.affiliation: Department of Anatomy, AIIMS, New Delhi, India.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Sharma
mesh_terms: D027321:Anion Transport Proteins / Q000235:genetics; D017920:Antiporters / Q000235:genetics; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D016022:Case-Control Studies; D024102:Collagen Type VIII / Q000235:genetics; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D016039:Corneal Transplantation; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C443712:COL8A2 protein, human; D024102:Collagen Type VIII; D018398:Homeodomain Proteins; C425809:SLC4A11 protein, human; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1