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

ABSTRACT: 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 thos

SUBMITTER: Roessler E 

PROVIDER: S-EPMC2774849 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature