Genetic Epilepsy

Gene: NDP

Green List (high evidence)

Genotype-phenotype correlation: unclear (Xiao H 2019). Dysruption of cysteine-knot motif corresponded to Norrie disease, noncysteine mutations are less severe (OMIM). Dickinson 2006, mentions that the same variant has been reported to cause different phenotypes. In addition, Gilmour DF mentions there’s high variable expressivity, as mutations in this gene can cause varying severity within the same family and even between eyes of the same individual.

Primarily XLR, but there are isolated cases of carrier females with varying degrees of retinal vasculature abnormalities (but not other aspects of Norrie disease) (Chen et al. 1993, Kondo et al. 2007).

Functional studies (Deng 2013) on various missense variants, including Cys substitutions, demonstrated defective Wnt singalling but the level of defect can vary. It is likely LoF mechanism, but there aren't many reports.

Created: 13 May 2020, 5:54 a.m. | Last Modified: 13 May 2020, 5:54 a.m.

Panel Version: 0.2814

Mode of inheritance
Other

Phenotypes
Exudative vitreoretinopathy 2, X-linked, MIM 305390; Norrie disease, MIM 310600

Publications

• 23444378
• 8268931
• 17325173
• 27217716
• 29181528
• 31827910

Red List (low evidence)

Predominantly an ocular phenotype, very rare reports of seizures.

Created: 24 Jan 2020, 9:21 a.m. | Last Modified: 24 Jan 2020, 9:21 a.m.

Panel Version: 0.365

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Norrie disease, MIM#310600

Publications

• 17334993