LRP5

Low-density lipoprotein receptor-related protein 5 is a protein that in humans is encoded by the LRP5 gene.[5][6][7] LRP5 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway. Mutations in LRP5 can lead to considerable changes in bone mass. A loss-of-function mutation causes osteoporosis-pseudoglioma (decrease in bone mass), while a gain-of-function mutation causes drastic increases in bone mass.

LRP5
Identifiers
Aliases	LRP5, BMND1, EVR1, EVR4, HBM, LR3, LRP-5, LRP7, OPPG, OPS, OPTA1, VBCH2, LDL receptor related protein 5, PCLD4, LRP-7
External IDs	OMIM: 603506 MGI: 1278315 HomoloGene: 1746 GeneCards: LRP5
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q13.2 Start 68,312,591 bp[1] End 68,449,275 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19|19 A Start 3,584,828 bp[2] End 3,686,564 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • toxin transporter activity • GO:0001948 protein binding • coreceptor activity involved in Wnt signaling pathway • Wnt-activated receptor activity • coreceptor activity involved in canonical Wnt signaling pathway • Wnt-protein binding Cellular component • integral component of membrane • Wnt signalosome • Wnt-Frizzled-LRP5/6 complex • membrane • receptor complex • cell membrane • endoplasmic reticulum • mitochondrion Biological process • regulation of apoptotic process • positive regulation of osteoblast proliferation • regulation of insulin secretion involved in cellular response to glucose stimulus • endocytosis • limb morphogenesis • extracellular matrix-cell signaling • branching involved in mammary gland duct morphogenesis • somatic stem cell population maintenance • bone marrow development • regulation of canonical Wnt signaling pathway • bone morphogenesis • gastrulation with mouth forming second • embryonic digit morphogenesis • positive regulation of sequence-specific DNA binding transcription factor activity • cell-cell signaling involved in mammary gland development • cholesterol metabolic process • Wnt signaling pathway • negative regulation of osteoblast differentiation • anatomical structure regression • mammary gland duct morphogenesis • regulation of blood pressure • positive regulation of transcription, DNA-templated • multicellular organism development • retina morphogenesis in camera-type eye • vasculature development • apoptotic process involved in blood vessel morphogenesis • positive regulation of mesenchymal cell proliferation • bone remodeling • Wnt signaling pathway involved in dorsal/ventral axis specification • glucose catabolic process • positive regulation of cell proliferation • retinal blood vessel morphogenesis • canonical Wnt signaling pathway • osteoblast development • negative regulation of protein serine/threonine kinase activity • adipose tissue development • cell migration involved in gastrulation • cholesterol homeostasis • bone development • positive regulation of fat cell differentiation • positive regulation of mitotic nuclear division • retina vasculature morphogenesis in camera-type eye • anterior/posterior pattern specification • positive regulation of transcription from RNA polymerase II promoter • regulation of bone remodeling • beta-catenin destruction complex disassembly • response to peptide hormone • positive regulation of osteoblast differentiation • toxin transport • Norrin signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4041	16973
Ensembl	ENSG00000162337	ENSMUSG00000024913
UniProt	O75197	Q91VN0
RefSeq (mRNA)	NM_001291902 NM_002335	NM_008513
RefSeq (protein)	NP_001278831 NP_002326	NP_032539
Location (UCSC)	Chr 11: 68.31 – 68.45 Mb	Chr 19: 3.58 – 3.69 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

LRP5 is a transmembrane low-density lipoprotein receptor that shares a similar structure with LRP6. In each protein, about 85% of its 1600-amino-acid length is extracellular. Each has four β-propeller motifs at the amino terminal end that alternate with four epidermal growth factor (EGF)-like repeats. Most extracellular ligands bind to LRP5 and LRP6 at the β-propellers. Each protein has a single-pass, 22-amino-acid segment that crosses the cell membrane and a 207-amino-acid segment that is internal to the cell.[8]

Function

LRP5 acts as a co-receptor with LRP6 and the Frizzled protein family members for transducing signals by Wnt proteins through the canonical Wnt pathway.[8] This protein plays a key role in skeletal homeostasis.[7]

Transcription

The LRP5 promoter contains binding sites for KLF15 and SP1.[9] In addition, 5' region of the LRP5 gene contains four RUNX2 binding sites.[10] LRP5 has been shown in mice and humans to inhibit expression of TPH1, the rate-limiting biosynthetic enzyme for serotonin in enterochromaffin cells of the duodenum[11][12][13][14][15][16] and that excess plasma serotonin leads to inhibition in bone. On the other hand, one study in mouse has shown a direct effect of Lrp5 on bone.[17]

Interactions

LRP5 has been shown to interact with AXIN1.[18][19]

Canonical WNT signals are transduced through Frizzled receptor and LRP5/LRP6 coreceptor to downregulate GSK3beta (GSK3B) activity not depending on Ser-9 phosphorylation.[20] Reduction of canonical Wnt signals upon depletion of LRP5 and LRP6 results in p120-catenin degradation.[21]

Clinical significance

The Wnt signaling pathway was first linked to bone development when a loss-of-function mutation in LRP5 was found to cause osteoporosis-pseudoglioma syndrome.[22] Shortly thereafter, two studies reported that gain-of-function mutations in LRP5 caused high bone mass.[23][24] Many bone density related diseases are caused by mutations in the LRP5 gene. There is controversy whether bone grows through Lrp5 through bone or the intestine.[25] The majority of the current data supports the concept that bone mass is controlled by LRP5 through the osteocytes.[26] Mice with the same Lrp5 gain-of-function mutations as also have high bone mass.[27] The high bone mass is maintained when the mutation only occurs in limbs or in cells of the osteoblastic lineage.[17] Bone mechanotransduction occurs through Lrp5[28] and is suppressed if Lrp5 is removed in only osteocytes.[29] There are promising osteoporosis clinical trials targeting sclerostin, an osteocyte-specific protein which inhibits Wnt signaling by binding to Lrp5.[26][30] An alternative model that has been verified in mice and in humans is that Lrp5 controls bone formation by inhibiting expression of TPH1, the rate-limiting biosynthetic enzyme for serotonin, a molecule that regulates bone formation, in enterochromaffin cells of the duodenum[11][12][13][14][15][16] and that excess plasma serotonin leads to inhibition in bone. Another study found that a different Tph1-inhibitor decreased serotonin levels in the blood and intestine, but did not affect bone mass or markers of bone formation.[17]

LRP5 may be essential for the development of retinal vasculature, and may play a role in capillary maturation.[31] Mutations in this gene also cause familial exudative vitreoretinopathy.[7]

A glial-derived extracellular ligand, Norrin, acts on a transmembrane receptor, Frizzled4, a coreceptor, Lrp5, and an auxiliary membrane protein, TSPAN12, on the surface of developing endothelial cells to control a transcriptional program that regulates endothelial growth and maturation.[32]

LRP5 knockout in mice led to increased plasma cholesterol levels on a high-fat diet because of the decreased hepatic clearance of chylomicron remnants. When fed a normal diet, LRP5-deficient mice showed a markedly impaired glucose tolerance with marked reduction in intracellular ATP and Ca²⁺ in response to glucose, and impairment in glucose-induced insulin secretion. IP3 production in response to glucose was also reduced in LRP5—islets possibly caused by a marked reduction of various transcripts for genes involved in glucose sensing in LRP5—islets. LRP5-deficient islets lacked the Wnt-3a-stimulated insulin secretion. These data suggest that WntLRP5 signaling contributes to the glucose-induced insulin secretion in the islets.[33]

In osteoarthritic chondrocytes the Wnt/beta-catenin pathway is activated with a significant up-regulation of beta-catenin mRNA expression. LRP5 mRNA and protein expression are also significantly up-regulated in osteoarthritic cartilage compared to normal cartilage, and LRP5 mRNA expression was further increased by vitamin D. Blocking LRP5 expression using siRNA against LRP5 resulted in a significant decrease in MMP13 mRNA and protein expressions. The catabolic role of LRP5 appears to be mediated by the Wnt/beta-catenin pathway in human osteoarthritis.[34]

The polyphenol curcumin increases the mRNA expression of LRP5.[35]

Mutations in LRP5 cause polycystic liver disease.[36]

References

1. GRCh38: Ensembl release 89: ENSG00000162337 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024913 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hey PJ, Twells RC, Phillips MS, Brown SD, Kawaguchi Y, Cox R, Dugan V, Hammond H, Metzker ML, Todd JA, Hess JF (Aug 1998). "Cloning of a novel member of the low-density lipoprotein receptor family". Gene. 216 (1): 103–11. doi:10.1016/S0378-1119(98)00311-4. PMID 9714764.
6. Chen D, Lathrop W, Dong Y (Feb 1999). "Molecular cloning of mouse Lrp7(Lr3) cDNA and chromosomal mapping of orthologous genes in mouse and human". Genomics. 55 (3): 314–21. doi:10.1006/geno.1998.5688. PMID 10049586.
7. "Entrez Gene: LRP5 low density lipoprotein receptor-related protein 5".
8. Williams BO, Insogna KL (Feb 2009). "Where Wnts went: the exploding field of Lrp5 and Lrp6 signaling in bone". Journal of Bone and Mineral Research. 24 (2): 171–8. doi:10.1359/jbmr.081235. PMC 3276354. PMID 19072724.
9. Li J, Yang Y, Jiang B, Zhang X, Zou Y, Gong Y (2010). "Sp1 and KLF15 regulate basal transcription of the human LRP5 gene". BMC Genetics. 11: 12. doi:10.1186/1471-2156-11-12. PMC 2831824. PMID 20141633.
10. Agueda L, Velázquez-Cruz R, Urreizti R, Yoskovitz G, Sarrión P, Jurado S, Güerri R, Garcia-Giralt N, Nogués X, Mellibovsky L, Díez-Pérez A, Marie PJ, Balcells S, Grinberg D (May 2011). "Functional relevance of the BMD-associated polymorphism rs312009: novel involvement of RUNX2 in LRP5 transcriptional regulation". Journal of Bone and Mineral Research. 26 (5): 1133–44. doi:10.1002/jbmr.293. PMID 21542013. S2CID 20985443.
11. Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G (Nov 2008). "Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum". Cell. 135 (5): 825–37. doi:10.1016/j.cell.2008.09.059. PMC 2614332. PMID 19041748.
12. Kode A, Mosialou I, Silva BC, Rached MT, Zhou B, Wang J, Townes TM, Hen R, DePinho RA, Guo XE, Kousteni S (Oct 2012). "FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin". The Journal of Clinical Investigation. 122 (10): 3490–503. doi:10.1172/JCI64906. PMC 3461930. PMID 22945629.
13. Frost M, Andersen TE, Yadav V, Brixen K, Karsenty G, Kassem M (Mar 2010). "Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin". Journal of Bone and Mineral Research. 25 (3): 673–5. doi:10.1002/jbmr.44. PMID 20200960. S2CID 24280062.
14. Rosen CJ (Feb 2009). "Breaking into bone biology: serotonin's secrets". Nature Medicine. 15 (2): 145–6. doi:10.1038/nm0209-145. PMID 19197289. S2CID 5489589.
15. Mödder UI, Achenbach SJ, Amin S, Riggs BL, Melton LJ, Khosla S (Feb 2010). "Relation of serum serotonin levels to bone density and structural parameters in women". Journal of Bone and Mineral Research. 25 (2): 415–22. doi:10.1359/jbmr.090721. PMC 3153390. PMID 19594297.
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17. Cui Y, Niziolek PJ, MacDonald BT, Zylstra CR, Alenina N, Robinson DR, Zhong Z, Matthes S, Jacobsen CM, Conlon RA, Brommage R, Liu Q, Mseeh F, Powell DR, Yang QM, Zambrowicz B, Gerrits H, Gossen JA, He X, Bader M, Williams BO, Warman ML, Robling AG (Jun 2011). "Lrp5 functions in bone to regulate bone mass". Nature Medicine. 17 (6): 684–91. doi:10.1038/nm.2388. PMC 3113461. PMID 21602802.
18. Mao J, Wang J, Liu B, Pan W, Farr GH, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D (Apr 2001). "Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway". Molecular Cell. 7 (4): 801–9. doi:10.1016/S1097-2765(01)00224-6. PMID 11336703.
19. Kim MJ, Chia IV, Costantini F (Nov 2008). "SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability". FASEB Journal. 22 (11): 3785–94. doi:10.1096/fj.08-113910. PMC 2574027. PMID 18632848.
20. Katoh M, Katoh M (Sep 2006). "Cross-talk of WNT and FGF signaling pathways at GSK3beta to regulate beta-catenin and SNAIL signaling cascades". Cancer Biology & Therapy. 5 (9): 1059–64. doi:10.4161/cbt.5.9.3151. PMID 16940750.
21. Hong JY, Park JI, Cho K, Gu D, Ji H, Artandi SE, McCrea PD (Dec 2010). "Shared molecular mechanisms regulate multiple catenin proteins: canonical Wnt signals and components modulate p120-catenin isoform-1 and additional p120 subfamily members". Journal of Cell Science. 123 (Pt 24): 4351–65. doi:10.1242/jcs.067199. PMC 2995616. PMID 21098636.
22. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, et al. (Nov 2001). "LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development". Cell. 107 (4): 513–23. doi:10.1016/S0092-8674(01)00571-2. PMID 11719191. S2CID 1631509.
23. Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Van Eerdewegh P, Recker RR, Johnson ML (Jan 2002). "A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait". American Journal of Human Genetics. 70 (1): 11–9. doi:10.1086/338450. PMC 419982. PMID 11741193.
24. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP (May 2002). "High bone density due to a mutation in LDL-receptor-related protein 5". The New England Journal of Medicine. 346 (20): 1513–21. doi:10.1056/NEJMoa013444. PMID 12015390.
25. Zhang W, Drake MT (Mar 2012). "Potential role for therapies targeting DKK1, LRP5, and serotonin in the treatment of osteoporosis". Current Osteoporosis Reports. 10 (1): 93–100. doi:10.1007/s11914-011-0086-8. PMID 22210558. S2CID 23718294.
26. Baron R, Kneissel M (Feb 2013). "WNT signaling in bone homeostasis and disease: from human mutations to treatments". Nature Medicine. 19 (2): 179–92. doi:10.1038/nm.3074. PMID 23389618. S2CID 19968640.
27. Babij P, Zhao W, Small C, Kharode Y, Yaworsky PJ, Bouxsein ML, Reddy PS, Bodine PV, Robinson JA, Bhat B, Marzolf J, Moran RA, Bex F (Jun 2003). "High bone mass in mice expressing a mutant LRP5 gene". Journal of Bone and Mineral Research. 18 (6): 960–74. doi:10.1359/jbmr.2003.18.6.960. PMID 12817748. S2CID 36863658.
28. Sawakami K, Robling AG, Ai M, Pitner ND, Liu D, Warden SJ, Li J, Maye P, Rowe DW, Duncan RL, Warman ML, Turner CH (Aug 2006). "The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment". The Journal of Biological Chemistry. 281 (33): 23698–711. doi:10.1074/jbc.M601000200. PMID 16790443.
29. Zhao L, Shim JW, Dodge TR, Robling AG, Yokota H (May 2013). "Inactivation of Lrp5 in osteocytes reduces young's modulus and responsiveness to the mechanical loading". Bone. 54 (1): 35–43. doi:10.1016/j.bone.2013.01.033. PMC 3602226. PMID 23356985.
30. Burgers TA, Williams BO (Jun 2013). "Regulation of Wnt/β-catenin signaling within and from osteocytes". Bone. 54 (2): 244–9. doi:10.1016/j.bone.2013.02.022. PMC 3652284. PMID 23470835.
31. Xia CH, Liu H, Cheung D, Wang M, Cheng C, Du X, Chang B, Beutler B, Gong X (Jun 2008). "A model for familial exudative vitreoretinopathy caused by LPR5 mutations". Human Molecular Genetics. 17 (11): 1605–12. doi:10.1093/hmg/ddn047. PMC 2902293. PMID 18263894.
32. Ye X, Wang Y, Nathans J (Sep 2010). "The Norrin/Frizzled4 signaling pathway in retinal vascular development and disease". Trends in Molecular Medicine. 16 (9): 417–25. doi:10.1016/j.molmed.2010.07.003. PMC 2963063. PMID 20688566.
33. Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, Takada S, Kim DH, Ioka RX, Ono M, Tomoyori H, Okubo M, Murase T, Kamataki A, Yamamoto J, Magoori K, Takahashi S, Miyamoto Y, Oishi H, Nose M, Okazaki M, Usui S, Imaizumi K, Yanagisawa M, Sakai J, Yamamoto TT (Jan 2003). "Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion". Proceedings of the National Academy of Sciences of the United States of America. 100 (1): 229–34. doi:10.1073/pnas.0133792100. PMC 140935. PMID 12509515.
34. Papathanasiou I, Malizos KN, Tsezou A (Mar 2010). "Low-density lipoprotein receptor-related protein 5 (LRP5) expression in human osteoarthritic chondrocytes". Journal of Orthopaedic Research. 28 (3): 348–53. doi:10.1002/jor.20993. PMID 19810105. S2CID 13525881.
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Further reading

• He X, Semenov M, Tamai K, Zeng X (Apr 2004). "LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way". Development. 131 (8): 1663–77. doi:10.1242/dev.01117. PMID 15084453.
• Godyna S, Liau G, Popa I, Stefansson S, Argraves WS (Jun 1995). "Identification of the low density lipoprotein receptor-related protein (LRP) as an endocytic receptor for thrombospondin-1". The Journal of Cell Biology. 129 (5): 1403–10. doi:10.1083/jcb.129.5.1403. PMC 2120467. PMID 7775583.
• Gong Y, Vikkula M, Boon L, Liu J, Beighton P, Ramesar R, Peltonen L, Somer H, Hirose T, Dallapiccola B, De Paepe A, Swoboda W, Zabel B, Superti-Furga A, Steinmann B, Brunner HG, Jans A, Boles RG, Adkins W, van den Boogaard MJ, Olsen BR, Warman ML (Jul 1996). "Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13". American Journal of Human Genetics. 59 (1): 146–51. PMC 1915094. PMID 8659519.
• Johnson ML, Gong G, Kimberling W, Reckér SM, Kimmel DB, Recker RB (Jun 1997). "Linkage of a gene causing high bone mass to human chromosome 11 (11q12-13)". American Journal of Human Genetics. 60 (6): 1326–32. doi:10.1086/515470. PMC 1716125. PMID 9199553.
• Dong Y, Lathrop W, Weaver D, Qiu Q, Cini J, Bertolini D, Chen D (Oct 1998). "Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity". Biochemical and Biophysical Research Communications. 251 (3): 784–90. doi:10.1006/bbrc.1998.9545. PMID 9790987.
• de Crecchio G, Simonelli F, Nunziata G, Mazzeo S, Greco GM, Rinaldi E, Ventruto V, Ciccodicola A, Miano MG, Testa F, Curci A, D'Urso M, Rinaldi MM, Cavaliere ML, Castelluccio P (Oct 1998). "Autosomal recessive familial exudative vitreoretinopathy: evidence for genetic heterogeneity". Clinical Genetics. 54 (4): 315–20. doi:10.1034/j.1399-0004.1998.5440409.x. PMID 9831343. S2CID 37420287.
• Mao J, Wang J, Liu B, Pan W, Farr GH, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D (Apr 2001). "Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway". Molecular Cell. 7 (4): 801–9. doi:10.1016/S1097-2765(01)00224-6. PMID 11336703.
• Twells RC, Metzker ML, Brown SD, Cox R, Garey C, Hammond H, Hey PJ, Levy E, Nakagawa Y, Philips MS, Todd JA, Hess JF (Mar 2001). "The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13". Genomics. 72 (3): 231–42. doi:10.1006/geno.2000.6492. PMID 11401438.
• Semënov MV, Tamai K, Brott BK, Kühl M, Sokol S, He X (Jun 2001). "Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6". Current Biology. 11 (12): 951–61. doi:10.1016/S0960-9822(01)00290-1. PMID 11448771. S2CID 15702819.
• Zorn AM (Aug 2001). "Wnt signalling: antagonistic Dickkopfs". Current Biology. 11 (15): R592–5. doi:10.1016/S0960-9822(01)00360-8. PMID 11516963. S2CID 14970864.
• Okubo M, Horinishi A, Kim DH, Yamamoto TT, Murase T (Feb 2002). "Seven novel sequence variants in the human low density lipoprotein receptor related protein 5 (LRP5) gene". Human Mutation. 19 (2): 186. doi:10.1002/humu.9012. PMID 11793484. S2CID 41880501.
• Van Hul E, Gram J, Bollerslev J, Van Wesenbeeck L, Mathysen D, Andersen PE, Vanhoenacker F, Van Hul W (Jun 2002). "Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13". Journal of Bone and Mineral Research. 17 (6): 1111–7. doi:10.1359/jbmr.2002.17.6.1111. PMID 12054167. S2CID 8308650.
• Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Bénichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, Warman ML, De Vernejoul MC, Bollerslev J, Van Hul W (Mar 2003). "Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density". American Journal of Human Genetics. 72 (3): 763–71. doi:10.1086/368277. PMC 1180253. PMID 12579474.

External links

• GeneReviews/NCBI/NIH/UW entry on Familial Exudative Vitreoretinopathy, Autosomal Dominant

This article incorporates text from the United States National Library of Medicine, which is in the public domain.