LRP5 gene

Overview
References

Overview

Gene (OMIM No.)	LRP5 (#603506)
Function of gene/protein	Protein: low density-lipoprotein receptor related protein 5 Forms a receptor complex with FZD4 as part of the Wnt/beta-catenin signaling pathway, which is required for tissue development including cell division and movement Important for retinal vascular growth, remodelling and maintenance Regulates bone mineral density
Clinical phenotype (OMIM phenotype no.)	Exudative vitreoretinopathy 4 (#601813) Osteoporosis-pseudoglioma syndrome (#259770) Both phenotypes may be part of a spectrum of the same disorder caused by mutations in LRP5
Inheritance	Autosomal dominant Autosomal recessive
Ocular features	Familial exudative vitreoretinopathy (FEVR) of variable severity Retrolental fibrotic mass Retinal folds extending from temporally from the disc to the anterior periphery Macula dragging Subretinal exudation Retinal neovascularisation Retinal breaks Rhegmatogenous or tractional retinal detachments
Systemic features	Reduced bone density/osteoporosis of variable severity
Key investigations	Fluorescein angiography to determine areas of non-perfusion in the peripheral retina Electrophysiology to determine visual potential B-scan USS to identify any posterior segment abnormalities (e.g retinal detachment) if presence of retrolental mass prevents a detailed fundal examination DEXA bone scan to assess bone density Developmental assessment
Molecular diagnosis	Next generation sequencing Targeted gene panels (Retinal) Whole exome sequencing Whole genome sequencing
Management	Ocular Laser to all areas of non-perfusion especially in eyes with visual potential Retinal detachments should be treated with an encircling buckle instead of a vitrectomy where possible; vitrectomy may be required for posterior breaks Systemic Medications for bone protection if osteoporosis is detected on DEXA scan
Therapies under research	None at present
Further information	Medline Plus

Jump to top

References

Narumi S, Numakura C, Shiihara T, et al. Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: Identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray. Am J Med Genet Part A 2010; 152A: 133–140
Gong Y, Slee RB, Fukai N, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001; 107: 513–523
Somer H, Palotie A, Somer M, et al. Osteoporosis-pseudoglioma syndrome: Clinical, morphological, and biochemical studies. J Med Genet 1988; 25: 543–549
Ai M, Heeger S, Bartels CF, et al. Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet 2005; 77: 741–753
He X, Semenov M, Tamai K, et al. LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling: Arrows point the way. Development 2004; 131: 1663–1677
Ye X, Wang Y, Cahill H, et al. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization [published correction appears in Cell. 2010 Apr 2;141(1):191]. Cell. 2009;139(2):285-298
Yadav VK, Ryu JH, Suda N, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 2008;135(5):825-837
Xiao H, Tong Y, Zhu Y, Peng M. Familial Exudative Vitreoretinopathy-Related Disease-Causing Genes and Norrin/β-Catenin Signal Pathway: Structure, Function, and Mutation Spectrums. J Ophthalmol. 2019:5782536
Toomes C, Bottomley HM, Jackson RM, et al. Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am J Hum Genet. 2004;74(4):721-730
Jiao X, Ventruto V, Trese MT, Shastry BS, Hejtmancik JF. Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5. Am J Hum Genet. 2004;75(5):878-884
Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H. Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. Hum Mutat. 2005;26(2):104-112
Gilmour DF. Familial exudative vitreoretinopathy and related retinopathies. Eye (Lond). 2015;29(1):1-14

Jump to top

Updated on January 18, 2021

Was this article helpful?

Yes No