Mutations in the candidate gene for Norrie disease

Abstract

Recently, we and others have isolated a candidate gene for X linked Norrie disease (ND) which was found to be deleted or disrupted in several patients. As a prerequisite for the identification of point mutations in the ND gene we have established the exon-intron structure of this gene. In 17 unrelated patients and 15 controls, PCR products derived from the promoter region, exons 1 and 2 as well as the coding part of exon 3 were analysed with the single strand conformation polymorphism (SSCP) technique. In 12 patients altered PCR fragments were detected which were studied in detail by direct sequencing. Eleven different mutations were found, and all but one are likely to give rise to significant structural changes in the predicted protein. These findings, and the absence of functionally relevant base changes in healthy controls, emphasize the causal role of this candidate gene in Norrie disease and pave the way for reliable diagnosis and carrier detection.

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

“…Direct sequencing of the NDG coding region and the splice sites between exons 2 and 3 was performed on PCR fragments 2B and 3 as described (Berger et al 1992 Linkage analysis was performed with LINKAGE version 5.1 (MLINK and LÏNKMAP), The gene frequency was set at 0.00002 and the penetrance at 100%. A two-point linkage was established with MLINK For all informative markers, whereas multipoint link age studies (with LINKMAP) were restricted to the following loci: OTC* DXS228, MAOB, NDG and DXS1003, The locus order and approximate distances were taken from the consensus map pub lished elsewhere (Schlessinger et ah 1993).…”

Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP

“…In addition, one family has been found to link to the EVR3 locus on chromosome 11p12-p13 [Downey et al, 2001]. Mutations in LRP5 have also been associated with arFEVR [Jiao et al, 2004], whereas X-linked recessive FEVR is caused by mutations in the Norrie disease gene (NDP) located on Xp11.3 [Berger et al, 1992b;Chen et al, 1993a]. The pathologic features of the disease initiate from the abnormal retinal development due to the incomplete vascularization of the peripheral retina and/or retinal blood vessel differentiation [Canny and Oliver, 1976].…”

“…Other ocular findings include the development of cataract, alterations in the composition of the vitreous body [Warburg, 1975], vitreoretinal hemorrhages, creation and deposition of retrolental fibrovascular tissue, retinal folding and detachment, accompanied by subretinal exudates [Enyedi et al, 1991;Polomeno et al, 1987], which are signs bearing high phenotypic overlap with FEVR [van Nouhuys, 1982]. ND is genetically homogeneous, and is caused by mutations in NDP [Berger et al, 1992b;Chen et al, 1993b].…”

NDP gene mutations in 14 French families with Norrie disease

“…So far, the gene product has an unknown function. Norrie disease was subsequently ascribed to mutations of the NDP gene (Berger et al, 1992b, Meindl et al, 1992.…”