ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000007.13) (NC_000007.14)
  • Haploinsufficiency score: 3
  • Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
  • Haploinsufficiency Phenotype: CURRARINO SYNDROME
Evidence for haploinsufficiency phenotype
PubMed ID Description
18449898 Cretolle et al. (2008) provide an update and review of MNX1 (formerly HLXB9) mutations in Currarino syndrome (CS). At the time, 66 different heterozygous cytogenetic or molecular anomalies at the MNX1 locus had been identified, including 7 nonsense mutations, two of which were novel to this particular report.
10749657 Hagan et al. (2000) report of MNX1 mutations in 22 patients with CS, including two probands with nonsense mutations and eight with frame shift mutations. Three probands were found to have hemizygous 7q36 microdeletions encompassing MNX1, analyzed by microsatellite typing; the actual sizes of these deletions were not determined.

Haploinsufficiency phenotype comments:

While focal deletions of MNX1 have not been reported, the association of truncating sequence-level MNX1 mutations with CS phenotypes comparable to those of patients with MNX1 microdeletions provides strong evidence that this disease results from haploinsufficiency.

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