PURPOSE: 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.
PURPOSE: 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: Konstantinos Nikopoulos; Christian Gilissen; Alexander Hoischen; C Erik van Nouhuys; F Nienke Boonstra; Ellen A W Blokland; Peer Arts; Nienke Wieskamp; Tim M Strom; Carmen Ayuso; Mauk A D Tilanus; Sanne Bouwhuis; Arijit Mukhopadhyay; Hans Scheffer; Lies H Hoefsloot; Joris A Veltman; Frans P M Cremers; Rob W J Collin Journal: Am J Hum Genet Date: 2010-02-12 Impact factor: 11.025
Authors: James A Poulter; Manir Ali; David F Gilmour; Aine Rice; Hiroyuki Kondo; Kenshi Hayashi; David A Mackey; Lisa S Kearns; Jonathan B Ruddle; Jamie E Craig; Eric A Pierce; Louise M Downey; Moin D Mohamed; Alexander F Markham; Chris F Inglehearn; Carmel Toomes Journal: Am J Hum Genet Date: 2010-02-12 Impact factor: 11.025
Authors: Rob W J Collin; Konstantinos Nikopoulos; Margo Dona; Christian Gilissen; Alexander Hoischen; F Nienke Boonstra; James A Poulter; Hiroyuki Kondo; Wolfgang Berger; Carmel Toomes; Tomoko Tahira; Lucas R Mohn; Ellen A Blokland; Lisette Hetterschijt; Manir Ali; Johanne M Groothuismink; Lonneke Duijkers; Chris F Inglehearn; Lea Sollfrank; Tim M Strom; Eiichi Uchio; C Erik van Nouhuys; Hannie Kremer; Joris A Veltman; Erwin van Wijk; Frans P M Cremers Journal: Proc Natl Acad Sci U S A Date: 2013-05-28 Impact factor: 11.205
Authors: Kamron Khan; Clare V Logan; Martin McKibbin; Eamonn Sheridan; Nursel H Elçioglu; Ozlem Yenice; David A Parry; Narcis Fernandez-Fuentes; Zakia I A Abdelhamed; Ahmed Al-Maskari; James A Poulter; Moin D Mohamed; Ian M Carr; Joanne E Morgan; Hussain Jafri; Yasmin Raashid; Graham R Taylor; Colin A Johnson; Chris F Inglehearn; Carmel Toomes; Manir Ali Journal: Hum Mol Genet Date: 2011-11-07 Impact factor: 6.150