ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Roessler et al. (PMID 19184110): This paper describes two truncating mutations (from two unrelated families) in individuals with holoprosencephaly-like features, both were inherited from normal parents. Rosenfeld (2011) (PMID 20951845): A focal deletion of DISP1 was reported and inherited from a normal parent. Also, based on clinical features present in patients whose 1q41q42 deletions do or do not include DISP1, the authors conclude that deletion of DISP1 is not sufficient to cause syndrome features seen with larger deletions. Rosenfeld et al (2010) (PMID: 20066439) identified patients who had CGH done who had a deletion of a loci or gene identified as a possibly associated with holoprosencephaly, either based on clinical reports or pathways. None of the patient identified with deletions including DISP1 had holoprosencephaly or a microform. Authors concluded that heterozygous loss is not sufficient for holoprosencephaly phenotypes. Though 3 independent mutations are described in DISP1, they have all been inherited from a normal parent and the expressivity and penetrance are not well understood.

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