title: Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5.
abstract: Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder that affects both the retina and vitreous body. Autosomal recessive FEVR was diagnosed in multiple individuals from three consanguineous families of European descent. A candidate-locus-directed genome scan shows linkage to the region on chromosome 11q flanked by markers D11S905 and D11S1314. The maximum LOD score of 3.6 at theta =0 is obtained with marker D11S987. Haplotype analysis confirms that the critical region is the 22-cM (311-Mb) interval flanked by markers D11S905 and D11S1314. This region contains LRP5 but not FZD4; mutations in both of these genes cause autosomal dominant FEVR. Sequencing of LRP5 shows, in all three families, homozygous mutations R570Q, R752G, and E1367K. This suggests that mutations in this gene can cause autosomal recessive as well as autosomal dominant FEVR.
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiao
authors.forename: Valerio
authors.initials: V
authors.lastname: Ventruto
authors.forename: Michael T
authors.initials: MT
authors.lastname: Trese
authors.forename: Barkur S
authors.initials: BS
authors.lastname: Shastry
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005192:Family Health; D005808:Genes, Recessive / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D026502:LDL-Receptor Related Proteins; D008126:Lod Score; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D011973:Receptors, LDL / Q000235:genetics*; D012164:Retinal Diseases / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014822:Vitreous Body / Q000473:pathology*; D044465:White People
chemical_list: D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D011973:Receptors, LDL