A mutation in the Norrie disease gene (NDP) associated with X–linked familial exudative vitreoretinopathy

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.

Secreted and Transmembrane Wnt Inhibitors and Activators

“…Evidence for a functional interaction between Norrin, Fz4, and LRP5 in vivo is provided by the finding that in humans, mutations in each gene cause familial exudative vitreoretinopathy (Chen et al 1993;Robitaille et al 2002;Toomes et al 2004a,b), an inherited disease characterized by peripheral retinal avascularity (Warden et al 2007). Consistent with the findings in human patients, targeted inactivation of Norrin, Fz4, or LRP5 in mice causes similar alterations in the retinal vascularization (Xu et al 2004;Luhmann et al 2005a;Xia et al 2008).…”

Linkage analysis in a Dutch family with X-linked recessive congenital stationary night blindness (XL-CSNB)

“…Therefore, at least formally, it is a possible candidate gene for CSNB. Clinically, the two dis orders are different but, on the other hand, the clinical pic ture of patients with mutations in NDG is by no means uniform (Chen et al 1993) and mild forms of the disease may exist. However, no sequence alterations have been detected within the open reading frame of NDG.…”

The Wnt pathway and the roles for its antagonists, DKKS, in angiogenesis

“…FEVR is a hereditary ocular disorder characterized by defective peripheral retinal vascularization, retinal detachment, and leaky vasculature that bleeds and exudes. Further investigation of this hereditary disorder has led to the finding that mutations in the Norrie gene result in symptoms similar to those produced by Fz-4 mutations (30). The Norrie gene encodes Norrin, a secreted protein with a CRD (31).…”