Mutations in VANGL1 associated with neural-tube defects.
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.
Kibar
Zoha
Z
Department of Biochemistry, McGill University, Montreal, QC, Canada.
Torban
Elena
E
McDearmid
Jonathan R
JR
Reynolds
Annie
A
Berghout
Joanne
J
Mathieu
Melissa
M
Kirillova
Irena
I
De Marco
Patrizia
P
Merello
Elisa
E
Hayes
Julie M
JM
Wallingford
John B
JB
Drapeau
Pierre
P
Capra
Valeria
V
Gros
Philippe
P
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
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