Abstract
Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by an abnormality of the peripheral retina. Both autosomal dominant (adFEVR) and X–linked (XLFEVR) forms have been described, but the biochemical defect(s) underlying the symptoms are unknown. Molecular analysis of the Norrie gene locus (NDP) in a four generation FEVR family (shown previously to exhibit linkage to the X–chromosome markers DXS228 and MAOA (Xp11.4–p11.3)) reveals a missense mutation in the highly conserved region of the NDP gene, which caused a neutral amino acid substitution (Leu124Phe), was detected in all of the affected males, but not in the unaffected family members, nor in normal controls. The observations suggest that phenotypes of both XLFEVR and Norrie disease can result from mutations in the same gene.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Criswick, V.G. & Schepens, C.L. Familial exudative vitreoretinopathy. Am. J. Ophthal. 68, 578–594 (1969).
Laqua, H. Familial exudative vitreoretinopathy. Graefes Arch. Klin. Exp. Ophthal. 213: 121–133 (1980).
Gow, J. & Oliver, G.L. Familial exudative vitreoretinopathy. Arch. Ophthal. 86, 150–155 (1971).
Van Nouhuys, C.E. Dominant exudative vitreoretinopathy and other vascular developmental disorders of the peripheral retina. Docum. Ophthal. 54, 1–414 (1982).
Feldman, E.L., Norris, J.L. & Cleasby, G.W. Autosomal dominant exudative vitreoretinopathy. Arch. Ophthal. 101, 1532–1535 (1983).
McKusick, V.A. Mendelian Inheritance in Man 9th edn (Johns Hopkins University Press, Baltimore, 1990).
Li, Y. et al. The Autosomal Dominant Familial Exudative Vitreoretinopathy Locus Maps on 11 q and is closely linked to D11S533. Am. J. hum. Genet. 51, 749–754 (1992).
Trese, M.X., Hartzer, M.K. & Shastry, B.S. X-chromosome linked forms of familial exudative vitreoretinopathy (XLFEVR). Invest. Ophthal. Vis. Sci. (abstract) 32, 692 (1991).
Plager, D.A., Orgel, I.K., Ellis, F.D., Hartzer, M., Trese, M.T. & Shastry, B.S., X-Unked Recessive Familial Exudative Vitreoretinopathy. Am. J. Ophthal. 114, 145–148 (1992).
Dudgeon, J. Familial exudative vitreo-retinopathy. Trans. Ophthal. Soc. U.K. 99, 45–49 (1979).
Fullwood, P. et al. X-Unked Exudative Vitreo-Retinopathy: Clinical Features and Genetic Linkage Analysis. Brit. J. Ophthal. 77, 168–170 (1993).
Warburg, M. Nome's disease. Atrophiabulborum hereditarium. ActaOphthal 39, 757–772 (1961).
Norrie, G. Causes of blindness in children. Acta Ophthal. 5, 357–386 (1927).
Bleeker-Wagemakers, E.M., Zweije-Hofman, I. & Gal, A. Norrie disease as part of a complex syndrome explained by a submicroscopic deletion of the X chromosome. Ophthal. Paed. Genet. 9, 137–142 (1988).
Sims, K.B. et al. Monoamineoxidase deficiency in males with an X chromosomal deletion. Neuron 2, 1069–1076 (1989).
Donnai, D., Mountford, R.C. & Read, A.P. Norrie disease resulting from a gene deletion: clinical features and DNA studies. J. med. Genet. 25, 73–78 (1988).
Zhu, D.P. et al. Microdeletion in the X-chromosome and prenatal diagnosis in a family with Norrie's disease. Am. J. med. Genet. 33, 485–488 (1989).
Sims, K.B. et al. The Norrie disease gene maps to a 150 kb region on chromosome Xp11.3. Hum. molec. Genet. 1, 83–89 (1992).
Chen, Z-Y. et al. Characterization of a YAC containing part or all of the Norrie disease locus. Hum. molec. Genet. 3, 161–164 (1992).
Berger, W. et al. Isolation of a candidate gene for Norrie disease by positional cloning. Nature Genet. 1, 199–203 (1992).
Chen, Z.-Y. et al. Isolation and characterization of a candidate gene for Norrie disease. Nature Genet. 1, 204–208 (1992).
Berger, W. et al. Mutations in the candidate gene for Norrie disease. Hum. molec. Genet. 1, 461–465 (1992).
Meindl, A. et al. Norrie disease is casued by mutations in an extracellular protein resembling C-terminal globular domain of mucins. Nature Genet. 2, 139–143 (1992).
Orita, M. et al. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc. natn. Acad. Sci. U.S.A. 86, 2766–2770 (1989).
Hittner, M.H. & Kretzer, F.L. Differential diagnosisofretinopathy of prematurity. In Retinopathy of prematurity: current concepts and controversies, (eds McPherson A.R. et al.) 53–66 (B.C. Decker, Toronto, 1986).
Pettenati, M.J. et al. Inversion (X) (p11.4q22) associated with Norrie Disease in a four generation family. Am. J. med. Genet. 45, 577–580 (1993).
Wells, J. et al. Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy. Nature Genet. 3, 213–218 (1993).
Nichols, B.E. et al. Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene. Nature Genet. 3, 202–207 (1993).
Kajiwara, K., Sandberg, M.A., Berson, E.L. & Dryja, T.P. A null mutation in the human peripherin/RDS gene in a family with autosomal dominant retinitis punctata albescens. Nature Genet. 3, 208–212 (1993).
Polomeno, R.C. et al. Norrie disease in a French-Canadian kindred: attempt to detect carriers by DNA analysis. Can. J. Opthal. 22, 21–23 (1987).
Parsons, M.A., Curtis, D., Blank, C.E., Hughes, H.N. & ScCartney, A.C.E. The ocular pathology of Norrie disease in a fetus of 11 weeks' gestational age. Graefe's Arch. Clin. Exp. Ophthal. 230, 248–251 (1992).
Chen, Z-Y. et al. Norrie disease gene: Characterization of deletions and possible function. Genomics 16, 533–535 (1993).
Voorberg, J. et al. Assembly and routing of von Willebrand factor variants: The requirements for disuffide-Olinked dimerization reside within thecarboxy-terminal 151 amino acids. J. cell. Bio. 113, 195–205 (1991).
Travis, G.H. & Helper, J.E. A medley of retinal dystrophies. Nature Genet. 3, 191–192 (1993).
Godel, V. et al. Primary retinal dysplasia transmitted as X-chromosome-linked recessive disorder. Am. J. Ophthal. 86, 221–227 (1978).
LaRussa, F. & Wesson, M.D. Norrie's disease vs. PHPV: one family's dilemma. J. Am. Optom. Assoc. 63, 404–408 (1992).
Chen, Z-Y., Powell, J.F., Hsu, Y-P.P., Breakefield, X.O. & Craig, I.W. Organization of the human monoamine oxidase genes and long-range physical mapping around them. Genomics. 14, 75–82 (1992).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chen, ZY., Battinelli, E., Fielder, A. et al. A mutation in the Norrie disease gene (NDP) associated with X–linked familial exudative vitreoretinopathy. Nat Genet 5, 180–183 (1993). https://doi.org/10.1038/ng1093-180
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng1093-180
This article is cited by
-
The role of PLVAP in endothelial cells
Cell and Tissue Research (2023)
-
Kinesin-5 Eg5 is essential for spindle assembly, chromosome stability and organogenesis in development
Cell Death Discovery (2022)
-
Retinopathy of prematurity: contribution of inflammatory and genetic factors
Molecular and Cellular Biochemistry (2022)
-
Retinoschisis and Norrie disease: a missing link
BMC Research Notes (2021)
-
Novel Norrie disease gene mutations in Chinese patients with familial exudative vitreoretinopathy
BMC Ophthalmology (2021)