Ndp, encoding Norrin cysteine knot growth factor, is located on the X chromosome. It is essential for normal intraretinal vascularisation, as the inner retina depends on the three intraretinal capillary plexi it influences [1,2].

Pathogenic variants in NDP can lead to diverse pathological phenotypes, mainly Norrie Disease (severe retinal phenotype with hearing loss) and Familial Exudative Vitreoretinopathy (FEVR, a moderate retinal phenotype) [1]. 201 different disease-causing variants in NDP have been reported. While previous reviews found no clear pattern in mutations causing FEVR or Norrie disease, mutations affecting cysteine residues and those causing early translation termination are associated with more severe Norrie disease phenotypes [1]. In female carriers of NDP-related retinopathies, most exhibit clinical features of FEVR despite it being an X-linked recessive disorder [2]. Also, novel NDP variants associated with FEVR have been identified, which expand the variant spectrum for genetic diagnosis [3]. In addition, two genetic variations in the NDP gene were found in Chinese families with X-linked Norrie disease, extending the mutational and phenotypic spectra [4].

In conclusion, Ndp is crucial for intraretinal vascular development. Studies on Ndp-related genetic variants contribute to understanding the mechanisms of Norrie disease and FEVR, providing valuable insights for the diagnosis and potential treatment of these ocular disorders.

References:

1. Wawrzynski, James, Patel, Aara, Badran, Abdul, Henderson, Robert, Sowden, Jane C. 2022. Spectrum of Mutations in NDP Resulting in Ocular Disease; a Systematic Review. In Frontiers in genetics, 13, 884722. doi:10.3389/fgene.2022.884722. https://pubmed.ncbi.nlm.nih.gov/35651932/

2. Huang, Li, Sun, Limei, Li, Xiaoyu, Zhang, Zhaotian, Ding, Xiaoyan. 2022. NDP-related retinopathies: clinical phenotype of female carriers. In The British journal of ophthalmology, 107, 1151-1155. doi:10.1136/bjophthalmol-2021-320084. https://pubmed.ncbi.nlm.nih.gov/35361573/

3. Peng, Yujiao, Zhao, Rulian, Dai, Erkuan, Li, Shujin, Yang, Mu. 2022. Whole-Exome Sequencing Reveals Novel NDP Variants in X-Linked Familial Exudative Vitreoretinopathy. In European journal of ophthalmology, 32, 3220-3226. doi:10.1177/11206721221074209. https://pubmed.ncbi.nlm.nih.gov/35037517/

4. Zhao, Xiangyu, Gao, Chunhai, Li, Lin, Che, Fengyuan, Liu, Qiji. . Clinical Exome Sequencing Identifies NDP Gene Variants in Two Chinese Families with X-Linked Norrie Disease. In Genetic testing and molecular biomarkers, 26, 589-594. doi:10.1089/gtmb.2022.0142. https://pubmed.ncbi.nlm.nih.gov/36577125/