title: A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects.
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.
authors.affiliation: 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.
authors.forename: June M
authors.initials: JM
authors.lastname: de la Cruz
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bamford
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Burdine
authors.forename: Erich
authors.initials: E
authors.lastname: Roessler
authors.forename: A James
authors.initials: AJ
authors.lastname: Barkovich
authors.forename: Dian
authors.initials: D
authors.lastname: Donnai
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
mesh_terms: 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
chemical_list: 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