Norrin Explained

Norrin, also known as Norrie disease protein or X-linked exudative vitreoretinopathy 2 protein (EVR2) is a protein that in humans is encoded by the NDP gene.^[1] Mutations in the NDP gene are associated with the Norrie disease.

Function

Signaling induced by the protein Norrin regulates vascular development of vertebrate retina and controls important blood vessels in the ear.^[1] Norrin binds with high affinity to Frizzled 4, and Frizzled 4 knockout mice exhibit abnormal vascular development of the retina.

Clinical significance

NDP is the genetic locus identified as harboring mutations that result in Norrie disease. Norrie disease is a rare genetic disorder characterized by bilateral congenital blindness that is caused by a vascularized mass behind each lens due to a maldeveloped retina (pseudoglioma).^[1]

Further reading

• Berger W, van de Pol D, Warburg M, etal . Mutations in the candidate gene for Norrie disease . Hum. Mol. Genet. . 1 . 7 . 461–5 . 1993 . 1307245 . 10.1093/hmg/1.7.461 .
• Black G, Redmond RM . The molecular biology of Norrie's disease . Eye . 8 . 5. 491–6 . 1995 . 7835440 . 10.1038/eye.1994.124. free .
• Masckauchán TN, Kitajewski J . Wnt/Frizzled signaling in the vasculature: new angiogenic factors in sight . Physiology . 21 . 3. 181–8 . 2007 . 16714476 . 10.1152/physiol.00058.2005 .
• Berger W, Meindl A, van de Pol TJ, etal . Isolation of a candidate gene for Norrie disease by positional cloning . Nat. Genet. . 1 . 3 . 199–203 . 1993 . 1303235 . 10.1038/ng0692-199 . 2718706 .
• Chen ZY, Hendriks RW, Jobling MA, etal . Isolation and characterization of a candidate gene for Norrie disease . Nat. Genet. . 1 . 3 . 204–8 . 1993 . 1303236 . 10.1038/ng0692-204 . 20354127 .
• Berger W, Meindl A, van de Pol TJ, etal . Isolation of a candidate gene for Norrie disease by positional cloning . Nat. Genet. . 2 . 1 . 84 . 1993 . 1303256 . 10.1038/ng0992-84a. free .
• Meindl A, Berger W, Meitinger T, etal . Norrie disease is caused by mutations in an extracellular protein resembling C-terminal globular domain of mucins . Nat. Genet. . 2 . 2 . 139–43 . 1993 . 1303264 . 10.1038/ng1092-139 . 25950198 .
• Shastry BS, Hejtmancik JF, Plager DA, etal . Linkage and candidate gene analysis of X-linked familial exudative vitreoretinopathy . Genomics . 27 . 2 . 341–4 . 1995 . 7558002 . 10.1006/geno.1995.1052 .
• Schuback DE, Chen ZY, Craig IW, etal . Mutations in the Norrie disease gene . Hum. Mutat. . 5 . 4 . 285–92 . 1995 . 7627181 . 10.1002/humu.1380050403 . 23519308 .
• Meindl A, Lorenz B, Achatz H, etal . Missense mutations in the NDP gene in patients with a less severe course of Norrie disease . Hum. Mol. Genet. . 4 . 3 . 489–90 . 1995 . 7795608 . 10.1093/hmg/4.3.489 .
• Joos KM, Kimura AE, Vandenburgh K, etal . Ocular findings associated with a Cys39Arg mutation in the Norrie disease gene . Arch. Ophthalmol. . 112 . 12 . 1574–9 . 1995 . 7993212 . 10.1001/archopht.1994.01090240080029.
• Fuchs S, Xu SY, Caballero M, etal . A missense point mutation (Leu13Arg) of the Norrie disease gene in a large Cuban kindred with Norrie disease . Hum. Mol. Genet. . 3 . 4 . 655–6 . 1994 . 8069314 . 10.1093/hmg/3.4.655 .
• Wong F, Goldberg MF, Hao Y . Identification of a nonsense mutation at codon 128 of the Norrie's disease gene in a male infant . Arch. Ophthalmol. . 111 . 11 . 1553–7 . 1993 . 8240113 . 10.1001/archopht.1993.01090110119036.
• Chen ZY, Battinelli EM, Fielder A, etal . A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy . Nat. Genet. . 5 . 2 . 180–3 . 1994 . 8252044 . 10.1038/ng1093-180 . 45016701 .
• Chen ZY, Battinelli EM, Woodruff G, etal . Characterization of a mutation within the NDP gene in a family with a manifesting female carrier . Hum. Mol. Genet. . 2 . 10 . 1727–9 . 1994 . 8268931 . 10.1093/hmg/2.10.1727 .
• Meitinger T, Meindl A, Bork P, etal . Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure . Nat. Genet. . 5 . 4 . 376–80 . 1994 . 8298646 . 10.1038/ng1293-376 . 29858707 .
• Strasberg P, Liede HA, Stein T, etal . A novel mutation in the Norrie disease gene predicted to disrupt the cystine knot growth factor motif . Hum. Mol. Genet. . 4 . 11 . 2179–80 . 1996 . 8589700 . 10.1093/hmg/4.11.2179 .
• Johnson K, Mintz-Hittner HA, Conley YP, Ferrell RE . X-linked exudative vitreoretinopathy caused by an arginine to leucine substitution (R121L) in the Norrie disease protein . Clin. Genet. . 50 . 3 . 113–5 . 1997 . 8946107 . 10.1111/j.1399-0004.1996.tb02363.x . 8690439 .

External links

• GeneReviews/NIH/NCBI/UW entry on NDP-Related Retinopathies

Notes and References

1. Web site: Entrez Gene: NDP Norrie disease (pseudoglioma).