Truncating loss-of-function mutations of DISP1 contribute to holoprosencephaly-like microform features in humans

Hum Genet. 2009 May;125(4):393-400. doi: 10.1007/s00439-009-0628-7. Epub 2009 Jan 31.


Defective function of the Sonic Hedgehog (SHH) signaling pathway is the most frequent alteration underlying holoprosencephaly (HPE) or its various clinical microforms. We performed an extensive mutational analysis of the entire human DISP1 gene, required for secretion of all hedgehog ligand(s) and which maps to the HPE 10 locus of human chromosome 1q41, as a HPE candidate gene. Here, we describe two independent families with truncating mutations in human DISP1 that resemble the cardinal craniofacial and neuro-developmental features of a recently described microdeletion syndrome that includes this gene; therefore, we suggest that DISP1 function contributes substantially to both of these signs in humans. While these clinical features are consistent with common HPE microforms, especially those linked to defective signaling by Sonic Hedgehog, we have insufficient evidence so far that functionally abnormal DISP1 alleles will commonly contribute to the more severe features of typical HPE.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • DNA Primers / genetics
  • Genetic Variation
  • Holoprosencephaly / genetics*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Patched Receptors
  • Phenotype
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Syndrome
  • Transfection


  • DNA Primers
  • Patched Receptors
  • Receptors, Cell Surface
  • Recombinant Proteins