Mutations in VANGL1 associated with neural-tube defects

N Engl J Med. 2007 Apr 5;356(14):1432-7. doi: 10.1056/NEJMoa060651.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Child
  • DNA Mutational Analysis
  • Dishevelled Proteins
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Italy
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Mutation, Missense*
  • Neural Tube Defects / genetics*
  • Pedigree
  • Phosphoproteins / metabolism
  • Risk Factors
  • Sequence Alignment

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Dishevelled Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Phosphoproteins
  • VANGL1 protein, human
  • VANGL2 protein, human