title: A novel mutation in the NR2E3 gene associated with Goldmann-Favre syndrome and vasoproliferative tumor of the retina.
abstract: OBJECTIVE
  Various autosomal recessive retinal dystrophies are reported to be associated with mutations in nuclear receptor subfamily 2, group E, member 3 (NR2E3, also called PNR) gene. The present study proposed to understand the clinical and genetic characteristics of the family of a patient with an ocular phenotype consistent with Goldmann-Favre syndrome (GFS) and vasoproliferative tumors of the retina (VPTRs).
  
  
  METHODS
  Twelve family members of the proband from three generations underwent complete ophthalmic examination, including best-corrected visual acuity with Snellen optotypes, tonometry, biomicroscopic examination, indirect ophthalmoscopy after pupillary dilatation, computerized perimetry, optical coherence tomography, fundus photography, intravenous fluorescein angiography, and electroretinography (ERG). All the study subjects underwent genetic analysis of the entire coding region of the NR2E3 gene with the bidirectional DNA sequencing approach. Hundred healthy individuals were screened for the variant.
  
  
  RESULTS
  The phenotype of the proband had features of GFS with VPTRs. The tumors showed complete resolution with cryotherapy and transpupillary thermotherapy (TTT). Sequencing of the entire coding region of the NR2E3 gene in the proband revealed a novel homozygous c.1117 A>G variant that led to the amino acid change from aspartic acid to glycine at position 406 (p.D406G). This change was present in the homozygous state in affected family members and in the heterozygous state in unaffected family members, and was undetectable in the control subjects. The identified novel p.D406G homozygous mutation was at an evolutionarily highly conserved region and may possibly affect the protein function (Sorting Intolerant From Tolerant [SIFT] score = 0.00).
  
  
  CONCLUSIONS
  Patients with GFS may present with retinal VPTRs that respond to therapy with cryotherapy and TTT. Molecular genetic studies helped to identify a novel p.D406G mutation in the affected members, which will aid in confirming the diagnosis, for genetic counseling of family members and potentially provide some form of therapy for the affected patients.
authors.affiliation: Department of Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore, Tamilnadu, India.
authors.forename: George J
authors.initials: GJ
authors.lastname: Manayath
authors.affiliation: Department of Genetics, Aravind Medical Research Foundation, Aravind Eye Hospital , Madurai, Tamilnadu, India.
authors.forename: Prasanthi
authors.initials: P
authors.lastname: Namburi
authors.affiliation: Department of Genetics, Aravind Medical Research Foundation, Aravind Eye Hospital , Madurai, Tamilnadu, India.
authors.forename: Sundaresan
authors.initials: S
authors.lastname: Periasamy
authors.affiliation: Department of Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore, Tamilnadu, India.
authors.forename: Jeevan A
authors.initials: JA
authors.lastname: Kale
authors.affiliation: Department of Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore, Tamilnadu, India.
authors.forename: Venkatapathy
authors.initials: V
authors.lastname: Narendran
authors.affiliation: Department of Ophthalmology, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Ganesh
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D004596:Electroretinography; D019143:Evolution, Molecular; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000503:physiopathology; D005190:Family; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D057093:Orphan Nuclear Receptors / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D019572:Retinal Neoplasms / Q000098:blood supply* / Q000235:genetics*; D014786:Vision Disorders / Q000235:genetics* / Q000503:physiopathology
chemical_list: C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors