HGNC Approved Gene Symbol: NYX
Cytogenetic location: Xp11.4 Genomic coordinates (GRCh38) : X:41,447,343-41,475,652 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| Xp11.4 | Night blindness, congenital stationary (complete), 1A, X-linked | 310500 | X-linked recessive | 3 |
By positional cloning and the candidate gene approach, directed at the elucidation of the defect in complete congenital stationary night blindness (CSNB1; 310500), Bech-Hansen et al. (2000) identified a novel gene, NYX, that encodes a protein (nyctalopin) of 481 amino acids. Nyctalopin shows sequence similarity with members of the superfamily of proteins containing tandem arrays of the leucine-rich repeat (LRR) motif, as well as other features qualifying the protein as a member of the subfamily of small leucine-rich proteoglycans (SLRPs). By PCR amplification of tissue-specific cDNA, Bech-Hansen et al. (2000) detected expression of NYX in retina and kidney only. In the retina it appeared to be expressed in photoreceptors, bipolar and amacrine interneurons, and ganglion cells.
Bech-Hansen et al. (2000) studied 22 families with X-linked complete CSNB and found 14 different mutations, including 1 founder mutation in 7 families from the United States, in the NYX gene.
Pusch et al. (2000) likewise detected 14 different mutations. In 3 families the gene was partially deleted. They found expression of the gene at low levels in retina, brain, testis, and muscle.
Gregg et al. (2003) studied the naturally occurring mouse mutant nob (no b-wave) to determine whether it provided an animal model for the complete form of human X-linked congenital stationary night blindness. They found that the nob phenotype was caused by an 85-bp deletion in the mouse Nyx gene. Behavioral testing showed that the nob mice had a significant decrease in visual sensitivity. Thus, they concluded, the nob mouse was a model for human CSNB1.
In 7 families from the United States, Bech-Hansen et al. (2000) found that the same in-phase 24-bp deletion was associated with X-linked complete congenital stationary night blindness (310500). The deletion was predicted to result in the loss of the 8 amino acids RACPAACA from the N-terminal cysteine cluster of nyctalopin. A genotype analysis of the X chromosomes with this deletion suggested that these families share a common founder mutation.
In 2 large pedigrees of Hispanic origin (from Costa Rica), Bech-Hansen et al. (2000) found that X-linked complete congenital stationary night blindness (310500) was associated with a trp350-to-ter (W350X) mutation in the NYX gene. This was predicted to eliminate the portion of nyctalopin required for establishing the GPI anchor, and potentially resulted in the protein being soluble rather than membrane-tethered.
In 4 families, Pusch et al. (2000) found that complete congenital stationary night blindness (310500) was associated with a cys35-to-ter (C35X) mutation in the NYX gene, resulting from a C-to-A transversion at nucleotide 105, changing TGC to TGA. No evidence for a founder allele was found for these families.
Pusch et al. (2000) found an ala187-to-lys (A187K) mutation in the NYX gene in affected members of 3 families from Sweden with congenital stationary night blindness (310500). They were found to share a common haplotype.
In affected members of a large Chinese family with congenital stationary night blindness (310500), Xiao et al. (2006) identified a 281G-C transversion in the NYX gene, resulting in an arg94-to-pro (R94P) substitution in the second leucine-rich repeat of the protein. The mutation was not identified in 96 control individuals.
In a Chinese boy with congenital stationary night blindness (310500), Xiao et al. (2006) identified a 302T-C transition in the NYX gene, resulting in an ile101-to-thr (I101T) substitution in the third leucine-rich repeat of the protein. Two additional male family members were affected, although molecular analysis was not performed. The mutation was not identified in 96 control individuals.
Bech-Hansen, N. T., Naylor, M. J., Maybaum, T. A., Sparkes, R. L., Koop, B., Birch, D. G., Bergen, A. A. B., Prinsen, C. F. M., Polomeno, R. C., Gal, A., Drack, A. V., Musarella, M. A., Jacobson, S. G., Young, R. S. L., Weleber, R. G. Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness. Nature Genet. 26: 319-323, 2000. [PubMed: 11062471] [Full Text: https://doi.org/10.1038/81619]
Gregg, R. G., Mukhopadhyay, S., Candille, S. I., Ball., S. L., Pardue, M. T., McCall, M. A., Peachey, N. S. Identification of the gene and the mutation responsible for the mouse nob phenotype. Invest. Ophthal. Vis. Sci. 44: 378-384, 2003. [PubMed: 12506099] [Full Text: https://doi.org/10.1167/iovs.02-0501]
Pusch, C. M., Zeitz, C., Brandau, O., Pesch, K., Achatz, H., Feil, S., Scharfe, C., Maurer, J., Jacobi, F. K., Pinckers, A., Andreasson, S., Hardcastle, A., Wissinger, B., Berger, W., Meindl, A. The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. Nature Genet. 26: 324-327, 2000. [PubMed: 11062472] [Full Text: https://doi.org/10.1038/81627]
Xiao, X., Jia, X., Guo, X., Li, S., Yang, Z., Zhang, Q. CSNB1 in Chinese families associated with novel mutations in NYX. J. Hum. Genet. 51: 634-640, 2006. [PubMed: 16670814] [Full Text: https://doi.org/10.1007/s10038-006-0406-5]