A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects

Hum Genet. 2002 May;110(5):422-8. doi: 10.1007/s00439-002-0709-3. Epub 2002 Apr 10.

Abstract

TDGF1 (CRIPTO) is an EGF-CFC family member and an obligate co-receptor involved in NODAL signaling, a developmental program implicated in midline, forebrain, and left-right axis development in model organisms. Previous studies of CFC1 (CRYPTIC), another member of the EGF-CFC family, demonstrated that normal function of this protein is required for proper laterality development in humans. Here we identify a mutation in the conserved CFC domain of TDGF1 in a patient with midline anomalies of the forebrain. The mutant protein is inactive in a zebrafish rescue assay, indicating a role for TDGF1 in human midline and forebrain development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Child, Preschool
  • Epidermal Growth Factor*
  • Female
  • GPI-Linked Proteins
  • Holoprosencephaly / genetics*
  • Homeodomain Proteins*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Membrane Glycoproteins*
  • Molecular Sequence Data
  • Mutation / genetics*
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / genetics*
  • Polymerase Chain Reaction
  • Prosencephalon / abnormalities*
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Transcription Factors*
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish Proteins*

Substances

  • GPI-Linked Proteins
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • TDGF1 protein, human
  • Transcription Factors
  • Zebrafish Proteins
  • tdgf1 protein, zebrafish
  • Epidermal Growth Factor