ZFIN ID: ZDB-PUB-020701-10
A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects
de la Cruz, J.M., Bamford, R.N., Burdine, R.D., Roessler, E., Barkovich, A.J., Donnai, D., Schier, A.F., and Muenke, M.
Date: 2002
Source: Human genetics   110(5): 422-428 (Journal)
Registered Authors: Burdine, Rebecca, Schier, Alexander
Keywords: none
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*
PubMed: 12073012 Full text @ Hum. Genet.
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.