ClinGen Dosage Sensitivity Curation Page

NHS

  • Curation Status: Complete

Location Information

  • Xp22.2-p22.13
  • GRCh37/hg19 chrX: 17,393,543-17,754,114
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr23: 17,375,200-17,735,994
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
14564667 Burdon et al. (2003) identify the gene responsible for Nance-Horan Sydnrome, which they name NHS. Loss of function mutations of NHS were identified in five families with Nance-Horan Syndrome, including four frameshift mutations resulting in a premature stop codon and a nonsense mutation. These mutations segregated with the disease in all families and were not seen in 200 control chromosomes.
15623749 Ramprasad et al. (2005) identified a nonsense mutation in the NHS gene in a four generation Asian-Indian family. The mutation was detected in all affected males and carrier females, but not in unaffected family members.
16736028 Florijn et al. (2006) test four families with Nance-horan syndrome for mutations in NHS. Two nonsense mutations, one frameshift mutation, and one splice-site mutation were identified.

Haploinsufficiency phenotype comments:

Loss of function mutations in males cause Nance-Horan syndrome characterized by congenital cataracts and microcornea, dental anomalies, large anteverted pinnae, and mild to moderate intellectual disability. Carrier females may show mild eye and teeth anomalies. Variable expressivity has been reported amongst affected members of the same family.

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.