The NDP gene provides instructions for making a protein called norrin. Norrin participates in chemical signaling pathways that affect the way cells and tissues develop. Studies suggest that norrin may play a role in Wnt signaling, which is important for cell division (proliferation), attachment of cells to one another (adhesion), cell movement (migration), and many other cellular activities.
Norrin is one of many proteins, or ligands, that can attach (bind) to other proteins called frizzled receptors. These receptors are embedded in the outer membranes of cells. Norrin binds with the receptor frizzled-4 (produced from the FZD4 gene), fitting together like a key in a lock. When a ligand binds to a frizzled receptor, it initiates a multi-step process that regulates the activity of certain genes.
The norrin protein and its receptor frizzled-4 participate in developmental processes that are believed to be crucial for normal development of the eye and other body systems. In particular, norrin seems to play critical roles in the specialization of cells in the retina (the thin layer at the back of the eye that senses light and color) and the establishment of a blood supply to the retina and the inner ear.
Health Conditions Related to Genetic Changes
Familial exudative vitreoretinopathy
Several NDP gene mutations have been found to cause the eye disorder familial exudative vitreoretinopathy. These mutations change single protein building blocks (amino acids) in the norrin protein, altering the normal folding of norrin or preventing it from binding to frizzled-4. The defective norrin disrupts chemical signaling in the developing eye, which interferes with the formation of blood vessels at the edges of the retina. The resulting abnormal blood supply to this tissue leads to retinal damage and vision loss in some people with familial exudative vitreoretinopathy.More About This Health Condition
More than 115 mutations in the NDP gene have been identified in people with Norrie disease. Norrie disease is an inherited eye disorder that leads to blindness in male infants at birth or soon after birth. NDP gene mutations that cause this condition affect the ability of the norrin protein to bind with frizzled-4, interfering with the specialization of retinal cells for their unique sensory function. As a result, masses of immature retinal cells accumulate in the back of the eyes. Disruption of norrin's role in the establishment of blood vessels supplying the eye eventually causes some of the tissues to break down.
Norrin is also expressed in other systems of the body, and the effects of the disorder can be widespread, including intellectual disability, seizures, behavioral problems, and delayed development. Specific abnormalities and their severity depend on the type and location of the NDP gene mutation. Mutations that delete portions of the NDP gene prevent production of norrin and result in severe problems affecting many body systems in addition to the eyes. Mutations that delete or change single amino acids usually result in less widespread effects.More About This Health Condition
Other retinal dystrophies
NDP gene mutations may cause other disorders that affect the retina. One mutation is associated with a disorder called Coats disease. This disorder causes leakage of blood vessels in the retina and retinal detachment, a condition in which layers of the retina separate, resulting in vision loss. Persistent hyperplastic primary vitreous (PHPV) is another retinal disorder that may be caused by NDP gene mutations. In persistent hyperplastic primary vitreous, a remnant of a blood vessel found in the eye before birth remains as a fibrous white stalk between the back of the eye and the lens. Persistent hyperplastic primary vitreous can cause vision loss through retinal detachment, cloudiness of the lens (cataract), or increased pressure inside the eye (glaucoma) that can damage the optic nerve.
In addition, NDP gene mutations may influence the course of a retinal disorder that affects some premature infants. Retinopathy of prematurity is a condition in which abnormal blood vessels appear in the retina and can cause retinal detachment. Babies with retinopathy of prematurity may experience improvement of the condition over time, but some NDP gene mutations have been associated with a worsening of the condition.
Other Names for This Gene
- Norrie disease (pseudoglioma)
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Chen ZY, Hendriks RW, Jobling MA, Powell JF, Breakefield XO, Sims KB, Craig IW. Isolation and characterization of a candidate gene for Norrie disease. Nat Genet. 1992 Jun;1(3):204-8. doi: 10.1038/ng0692-204. Citation on PubMed
- Clevers H. Wnt signaling: Ig-norrin the dogma. Curr Biol. 2004 Jun 8;14(11):R436-7. doi: 10.1016/j.cub.2004.05.039. Citation on PubMed
- Dickinson JL, Sale MM, Passmore A, FitzGerald LM, Wheatley CM, Burdon KP, Craig JE, Tengtrisorn S, Carden SM, Maclean H, Mackey DA. Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity. Clin Exp Ophthalmol. 2006 Sep-Oct;34(7):682-8. doi: 10.1111/j.1442-9071.2006.01314.x. Citation on PubMed
- Haider MZ, Devarajan LV, Al-Essa M, Kumar H. A C597-->A polymorphism in the Norrie disease gene is associated with advanced retinopathy of prematurity in premature Kuwaiti infants. J Biomed Sci. 2002 Jul-Aug;9(4):365-70. doi: 10.1007/BF02256593. Citation on PubMed
- Hiraoka M, Berinstein DM, Trese MT, Shastry BS. Insertion and deletion mutations in the dinucleotide repeat region of the Norrie disease gene in patients with advanced retinopathy of prematurity. J Hum Genet. 2001;46(4):178-81. doi: 10.1007/s100380170085. Citation on PubMed
- Kondo H, Qin M, Kusaka S, Tahira T, Hasebe H, Hayashi H, Uchio E, Hayashi K. Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy. Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1276-82. doi: 10.1167/iovs.06-1042. Citation on PubMed
- Royer G, Hanein S, Raclin V, Gigarel N, Rozet JM, Munnich A, Steffann J, Dufier JL, Kaplan J, Bonnefont JP. NDP gene mutations in 14 French families with Norrie disease. Hum Mutat. 2003 Dec;22(6):499. doi: 10.1002/humu.9204. Citation on PubMed
- Scruggs BA, Reding MQ, Schimmenti LA. NDP-Related Retinopathies. 1999 Jul 30 [updated 2023 Mar 23]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK1331/ Citation on PubMed
- Shastry BS. Genetic susceptibility to advanced retinopathy of prematurity (ROP). J Biomed Sci. 2010 Aug 25;17(1):69. doi: 10.1186/1423-0127-17-69. Citation on PubMed or Free article on PubMed Central
- Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004 Mar 19;116(6):883-95. doi: 10.1016/s0092-8674(04)00216-8. Citation on PubMed
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