2005, Number 1
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ABSTRACTNorrie disease (ND) is characterized by congenital blindness due to proliferative and degenerative changes in retina and vitreous. One third of the patients harbor mental retardation and neurosensorial deafness. ND can be diagnosed after birth by the presence of leukocoria caused by anomalies in retrolental structures. Although ND is transmitted as an X-linked recessive trait, some female carriers can show ocular anomalies. ND gene is on Xp11.3-11.4 and spans 600 kb. Most of the patients present point mutations while a minor number of patients have deletions in the ND locus. In the present study, we analyzed a family with ND, which presented clinical variability. We also point out that it is important to establish a correct diagnosis and to identify the molecular defect in the ND gene in order to detect carriers and offer a correct genetic counseling.
Townes PL, Roca PD. Norrie disease (Hereditary oculo-acustic-cerebral degeneration). Report of a United States family. Am J Ophthalmol 1973; 76:797-803.
2. Apple DJ, Fishman GA, Goldberg MF. Ocular histopathology of Norrie’s disease. Am J Ophthalmol 1974; 78:196-203.
3. Enyedi LB, de Juan E, Gaitan A. Ultrastructural study of Norrie’s disease. Am J Ophthalmol 1991; 111:439-445.
4. Warburg M. Norrie’s disease. J Ment Defic Res 1968; 12:247-251.
5. Berger W, Van de Pol D, Warburg M y cols. Mutations in the candidate gene for Norrie disease. Hum Mol Genet 1992; 1:461-465.
6. Meindl A, Berger W, Meitinger T y cols. Norrie disease is caused by mutations in an extracellular protein resembling C-terminal globular domain of mucins. Nat Genet 1992; 2:139-143.
7. Berger W. Molecular dissection of Norrie disease. Acta Anatomica 1998; 162:95-100.
8. Johnson K, Mintz-Histtner HA, Conley YP Ferrel RE. X-linked exudative vitreoretinopathy caused by an arginine to leucine substitution (R121L) in the Norrie disease protein. Clin Genet 1996; 50:113-115.
9. Torrente I, Mangino M, Gennareli M y cols. Two new missense mutations (A105T and C110G) in the norrin gene in two families with Norrie disease and familial exudative vitreo-retinopathy. Am J Med Genet 1997; 72:242-244.
10. Shastry BS, Pendergast SD, Hartzer MK, Liu X, Trese M. Identification of missense mutations in the Norrie disease gene associated with Retinopathy of prematurity. Arch Ophthalmol 1997; 115:651-655.
11. Black GCM, Perveen R, Bonshek R y cols. Coats disease of the retina (unilateral retinal telangiectasis) caused by somatic mutation in the NDP gene: a role for norrin in retinal angiogenesis. Hum Mol Genet 1999; 8:2031-2035.
12. Talks SJ, Ebenezer N, Hykin P y cols. De novo mutations in the 5’ regulatory region of the Norrie disease gene in retinopathy of prematurity. J Med Genet 2000; 38:46-52.
13. Voorberg J, Fontijn R, Calafat J, Janssen H, van Mourik JA, Pannekoek H. Assembly and routing of von Willebrand factor variants: the requirements for disulphide-linked dimerization reside within the carboxy-terminal 151 amino acids. J Cell Biol 1991; 113:195-205.
14. Meitinger T, Meindl A, Bork P y cols. Molecular modeling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure. Nat Genet 1993; 5:376-380.
15. Perez-Vilar J, Hill RL. Norrie disease protein (Norrin) forms disulfide-linked oligomers associated with the extracellular matrix. J Biol Chem 1997; 272:33410-5.
16. Mintz-Hittner HA, Ferrell RE, Sims KB y cols. Peripheral retinopathy in offspring of carriers of Norrie disease gene mutations: Possible transplacental effect on abnormal norrin. Ophthalmology 1996; 103:2128-2134.
17. Vitt UA, Hsu SY, Hsueh AJW. Evolution and classification of cystine knot-containing hormones and related extracellular signaling molecules. Mol Endocrinol 2001; 15:681-694.
18. Rehm HL, Zhang D-S, Brown MC y cols. Vascular defects and sensorineural deafness in a mouse model of Norrie disease. J Neuroscience 2002; 22:4286-92.
19. Moreira-Filho CA, Neustein I. A presumptive new variant of Norrie’s disease. J Med Genet 1979; 16:125-128.
20. Donnai D, Mountford RC, Read AP. Norrie disease resulting from a gene deletion: Clinical features and DNA studies. J Med Genet 1988; 25:73-78.
21. Meindl A, Lorenz B, Achatz H, Hellebrand H, Schmitz-Valckenberg P, Meitinger T. Missense mutations in the NDP gene in patients with a less severe course of Norrie disease. Hum Mol Genet 1995; 4:489-490.
22. Shastry BS, Hejtmancik JF, Plager DA, Hartzer MK, Trese MT. Linkage and candidate gene analysis of X-linked familial exudative vitreoretinopathy. Genomics 1995; 27:341-344.