title: Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q.
abstract: Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder of the retinal vascular system. Autosomal dominant FEVR is genetically heterogeneous, but its principal locus, EVR1, is on chromosome 11q13-q23. The gene encoding the Wnt receptor frizzled-4 (FZD4) was recently reported to be the EVR1 gene, but our mutation screen revealed fewer patients harboring mutations than expected. Here, we describe mutations in a second gene at the EVR1 locus, low-density-lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor. This finding further underlines the significance of Wnt signaling in the vascularization of the eye and highlights the potential dangers of using multiple families to refine genetic intervals in gene-identification studies.
authors.affiliation: Molecular Medicine Unit, University of Leeds, Leeds, United Kingdom. c.toomes@leeds.ac.uk
authors.forename: Carmel
authors.initials: C
authors.lastname: Toomes
authors.forename: Helen M
authors.initials: HM
authors.lastname: Bottomley
authors.forename: Richard M
authors.initials: RM
authors.lastname: Jackson
authors.forename: Katherine V
authors.initials: KV
authors.lastname: Towns
authors.forename: Sheila
authors.initials: S
authors.lastname: Scott
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.forename: Richard
authors.initials: R
authors.lastname: Trembath
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Woodruff
authors.forename: Cheryl Y
authors.initials: CY
authors.lastname: Gregory-Evans
authors.forename: Kevin
authors.initials: K
authors.lastname: Gregory-Evans
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parker
authors.forename: Graeme C M
authors.initials: GC
authors.lastname: Black
authors.forename: Louise M
authors.initials: LM
authors.lastname: Downey
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D051157:Frizzled Receptors; D006801:Humans; D007438:Introns / Q000235:genetics; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics*; D012164:Retinal Diseases / Q000235:genetics* / Q000473:pathology
chemical_list: C402930:FZD4 protein, human; D051157:Frizzled Receptors; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011973:Receptors, LDL