NDP

• Haploinsufficiency score: 3
• Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
• Haploinsufficiency Phenotype: NORRIE DISEASE; ND

Evidence for haploinsufficiency phenotype

PubMed ID	Description
8790105	In a boy with Norrie disease, Chynn et al. (1996) identified a 1-bp deletion in codon 35 of the NDP gene. The deletion resulted in a frameshift and a premature stop at codon 40 (out of 133 codons). The unaffected mother was heterozygous for the mutation.
1301161	In a family with 2 members affected with Norrie disease, Walker et al. (1997) identified a C-to-A transversion in exon 3 of the NDP gene, resulting in a nonsense mutation at amino acid 73 (S73X). NDP encodes a 133 amino acid protein. The authors state that this mutation is predicted to produce a nonfunctional truncated protein.
1307245	Berger et al. (1992) identified 11 different mutations in the NDP gene in 17 unrelated patients with Norrie disease. These include 5 missense mutations, 2 nonsense mutations (S57X and C110X, respectively), 2 1-bp deletions, 1 4-bp insertion, and 1 splice site mutation. These mutations were not identified in 15 healthy male controls.

Haploinsufficiency phenotype comments:

X-linked recessive mutations in NDP cause Norrie disease

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.