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Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4 , LRP5 , and NDP
Author(s) -
Nikopoulos Konstantinos,
Venselaar Hanka,
Collin Rob W.J.,
RiveiroAlvarez Rosa,
Boonstra F. Nienke,
Hooymans Johanna M.M.,
Mukhopadhyay Arijit,
Shears Deborah,
van Bers Marleen,
de Wijs Ilse J.,
van Essen Anthonie J.,
Sijmons Rolf H.,
Tilanus Mauk A.D.,
van Nouhuys C. Erik,
Ayuso Carmen,
Hoefsloot Lies H.,
Cremers Frans P.M.
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21250
Subject(s) - biology , wnt signaling pathway , lrp5 , frizzled , missense mutation , genetics , phenotype , mutation , gene , cancer research , microbiology and biotechnology
Wnt signaling is a crucial component of the cell machinery orchestrating a series of physiological processes such as cell survival, proliferation, and migration. Among the plethora of roles that Wnt signaling plays, its canonical branch regulates eye organogenesis and angiogenesis. Mutations in the genes encoding the low density lipoprotein receptor protein 5 ( LRP5 ) and frizzled 4 ( FZD4 ), acting as coreceptors for Wnt ligands, cause familial exudative vitreoretinopathy (FEVR). Moreover, mutations in the gene encoding NDP, a ligand for these Wnt receptors, cause Norrie disease and FEVR. Both FEVR and Norrie disease share similar phenotypic characteristics, including abnormal vascularization of the peripheral retina and formation of fibrovascular masses in the eye that can lead to blindness. In this mutation update, we report 21 novel variants for FZD4 , LRP5 , and NDP , and discuss the putative functional consequences of missense mutations. In addition, we provide a comprehensive overview of all previously published variants in the aforementioned genes and summarize the phenotypic characteristics in mouse models carrying mutations in the orthologous genes. The increasing molecular understanding of Wnt signaling, related to ocular development and blood supply, offers more tools for accurate disease diagnosis that may be important in the development of therapeutic interventions. Hum Mutat 31:656–666, 2010. © 2010 Wiley‐Liss, Inc.