title: Clinical and molecular evaluation of probands and family members with familial exudative vitreoretinopathy.
abstract: OBJECTIVE
  To describe the ophthalmic characteristics and to identify the molecular cause of FEVR in a cohort of Dutch probands and their family members.
  
  
  METHODS
  Twenty families with familial exudative vitreoretinopathy (FEVR) comprising 83 affected and nonaffected individuals were studied. Based on the presence of an avascular zone, the clinical diagnosis was made and biometric data of the posterior pole of 57 patients and family members were obtained by the analysis of fundus photographs and compared with the data of 40 controls. The FZD4, LRP5, and NDP genes were screened for mutations in one affected individual per family. The segregation of the gene variants was studied in the corresponding families.
  
  
  RESULTS
  Forty of 83 individuals showed an avascular zone, the most evident clinical sign of FEVR, five showed major signs of FEVR, and 38 persons were not clinically affected. Compared with the control subjects the patients with FEVR had a significantly larger disc-to-macula distance and a significantly smaller optic disc. In 8 of 20 families, a FZD4 mutation was identified, in 2 a mutation in the LRP5 gene, and in 2 a mutation in the NDP gene. Three known and five novel mutations were identified. Nonpenetrance was observed in 26% of the mutation carriers.
  
  
  CONCLUSIONS
  Significant anatomic differences were identified between the eyes of patients with FEVR with an avascular zone, when compared with those of the control subjects. In patients with an avascular zone, the optic disc was smaller and the disc-to-macula distance larger than in the control subjects. In 60% of the probands, mutations were identified in one of the three known FEVR genes.
authors.affiliation: Bartiméus Institute for the Visually Impaired, Zeist, The Netherlands. n.boonstra@bartimeus.nl
authors.forename: F Nienke
authors.initials: FN
authors.lastname: Boonstra
authors.forename: C Erik
authors.initials: CE
authors.lastname: van Nouhuys
authors.forename: José
authors.initials: J
authors.lastname: Schuil
authors.forename: Ilse J
authors.initials: IJ
authors.lastname: de Wijs
authors.forename: Kim P
authors.initials: KP
authors.lastname: van der Donk
authors.forename: Kostas
authors.initials: K
authors.lastname: Nikopoulos
authors.forename: Arijit
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Hans
authors.initials: H
authors.lastname: Scheffer
authors.forename: Mauk A D
authors.initials: MA
authors.lastname: Tilanus
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot