ClinGen Dosage Sensitivity Curation Page

NYX

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
11062472 Pusch CM et al (2000) did genetic mapping in families with X-linked complete congenital stationary night blindness (XLCSNB) and found the subtype of complete CSNB (CSNB1 or cCSNB) locus has been mapped to Xp11.4, and leading to identification of a new gene mutated in CSNB1 patients, NYX. It is partially deleted in 3 families: exon 1 and 2 (maximum size of deletion is 10kb) deleted in family 2676 and had 21 segregation in this family; exon 3 and 3?-UTR deletion which predicted causing truncated protein in family 7903; and a 326 bp deletion which predicted causing truncated protein in family CSNBX. Mutation analysis in a further 21 families detected another 13 different mutations, including a nonsense mutation C35X in family 5884.
11062471 Bech-Hansen NT et al (2000) studied 22 families with ?complete? X-linked CSNB (CSNB1, OMIM 310500) and found 14 different mutations, including one founder mutation, a 24 bp deletion, p.Arg29_Ala36del, identified in 7 families originating from the USA with a common founder. One of the 7 families had 5 segregations. A W350X nonsense mutation was found in 2 families, in which had 2 segregations and 1 segregation, respectively.
18617546 Leroy BP et al (2009) studied probands with cCSNB from three unrelated large Flemish families from Belgium. DNA was extracted from peripheral blood, and the coding region of NYX along with parts of the 5'UTR and 3'UTR and intronic regions covering the splice sites were PCR amplified and sequenced. In the affected individuals of three Flemish families with the complete form of CSNB a novel NYX mutation, c.855delG was identified. This deletion is predicted to lead to a frameshift mutation, p.Asp286ThrfsX62 causing a premature stop codon. Two of the families >7 segregations, one family =6 segregations. PMID 22183355, Lodha N et al (2012). In a cohort of 199 patients diagnosed clinically with CSNB, 73 were diagnosed with X-inked cCSNB. They identified a total of 32 unique mutations in NYX, among which a 24-bp deletion resulted in the loss of the RACPAACA amino acids in the N-terminal Cys-rich region of nyctalopin, was detected in 12 North American Caucasian CSNB families.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.