title: Mutations in VANGL1 associated with neural-tube defects.
abstract: Neural-tube defects such as anencephaly and spina bifida constitute a group of common congenital malformations caused by complex genetic and environmental factors. We have identified three mutations in the VANGL1 gene in patients with familial types (V239I and R274Q) and a sporadic type (M328T) of the disease, including a spontaneous mutation (V239I) appearing in a familial setting. In a protein-protein interaction assay V239I abolished interaction of VANGL1 protein with its binding partners, disheveled-1, -2, and -3. These findings implicate VANGL1 as a risk factor in human neural-tube defects.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, QC, Canada.
authors.forename: Zoha
authors.initials: Z
authors.lastname: Kibar
authors.forename: Elena
authors.initials: E
authors.lastname: Torban
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: McDearmid
authors.forename: Annie
authors.initials: A
authors.lastname: Reynolds
authors.forename: Joanne
authors.initials: J
authors.lastname: Berghout
authors.forename: Melissa
authors.initials: M
authors.lastname: Mathieu
authors.forename: Irena
authors.initials: I
authors.lastname: Kirillova
authors.forename: Patrizia
authors.initials: P
authors.lastname: De Marco
authors.forename: Elisa
authors.initials: E
authors.lastname: Merello
authors.forename: Julie M
authors.initials: JM
authors.lastname: Hayes
authors.forename: John B
authors.initials: JB
authors.lastname: Wallingford
authors.forename: Pierre
authors.initials: P
authors.lastname: Drapeau
authors.forename: Valeria
authors.initials: V
authors.lastname: Capra
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004252:DNA Mutational Analysis; D000072261:Dishevelled Proteins; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007558:Italy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009436:Neural Tube Defects / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000378:metabolism; D012307:Risk Factors; D016415:Sequence Alignment
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000072261:Dishevelled Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C488287:VANGL1 protein, human; C468513:VANGL2 protein, human