A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects.
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.
de la Cruz
June M
JM
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, MSC 1852, Building 10 Room 10C103, Bethesda, MD 20892-1852, USA.
Bamford
Richard N
RN
Burdine
Rebecca D
RD
Roessler
Erich
E
Barkovich
A James
AJ
Donnai
Dian
D
Schier
Alexander F
AF
Muenke
Maximilian
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002675:Child, Preschool; D004815:Epidermal Growth Factor; D005260:Female; D058851:GPI-Linked Proteins; D016142:Holoprosencephaly / Q000235:genetics*; D018398:Homeodomain Proteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016548:Prosencephalon / Q000002:abnormalities*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins
D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human; D014157:Transcription Factors; D029961:Zebrafish Proteins; C110484:tdgf1 protein, zebrafish; D004815:Epidermal Growth Factor