CANDIDATE PLANAR CELL POLARITY (PCP) GENE ANALYSIS IN HUMAN NEURAL TUBE DEFECTS (NTDs)
- 3 Years 2008/2011
- 260.062€ Total Award
Neural Tube Defects (NTDs) are severe congenital malformations characterized by a failure of neural tube closure during early embryonic development. Failed closure at the cranial neural tube, known as anencephaly, is a lethal condition, whereas failed closure at the spinal region results in a myelomeningocele. Consequences of this birth defect range from minor defects that can be corrected by surgery to severe physical deformations and paralysis. NTDs occur in 1 out every 1,000 pregnancies and they represent the second cause of death after congenital heart defects. Animal models have provided crucial mechanistic information and possible candidate genes to explain susceptibility to NTDs. A survey of the genes whose disruption causes NTD indicates multiple key signaling pathways and cellular functions that are essential for neural tube closure. The gene VANGL1, that was found mutated in three NTDs children, codes for a membrane protein that enables cells to orient themselves properly, during early steps of development. The presence of mutations cause cells to lose their correct orientation, so the tissue in which it is expressed fails to develop properly, causing gaps that leave nerve tissue exposed. This finding encourage to extend the investigation to other proteins that, with VANGL1, play a role to determine the correct cell orientation during development. In fact, probably VANGL1 has just a partial role in the pathogenesis of NTDs, and alterations in more than one gene are causative. This research will provide us a better understanding of molecular mechanisms underlying NTDs. Moreover, the gain of our knowledge could help us in the diagnosis, by the identification of parents who have a higher chance of an affected child. Actually, we are far to have immediate clinical benefits for NTDs, but providing clinicians with a better knowledge of the development of the disease, we could speed up the search for a focused prevention and a more complete familial counseling.
Scientific Publications
- 2012 BIRTH DEFECTS RES A
Role of the planar cell polarity gene CELSR1 in neural tube defects and caudal agenesis
- 2013 BIRTH DEFECTS RES A
Rare missense variants in DVL1, one of the human counterparts of the Drosophila dishevelled gene, do not confer increased risk for Neural Tube Defects
- 2014 BIRTH DEFECTS RES A
Planar Cell Polarity Gene Mutations Contribute to the Etiology of Human Neural Tube Defects in Our Population
- 2015 BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
Role of the planar cell polarity gene Protein tyrosine kinase 7 in neural tube defects in humans
- 2012 HUMAN MUTATION
FZD6 is a Novel Gene for Human Neural Tube Defects
- 2010 MECHANISMS OF DEVELOPMENT
VANGL1 rare variants associated with neural tube defects affect convergent extension in zebrafish
- 2013 JOURNAL OF MOLECULAR NEUROSCIENCE
Genetic Analysis of Disheveled 2 and Disheveled 3 in Human Neural Tube Defects
- 2011 HUMAN MUTATION
Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects
- 2011 BIOFACTORS
Human neural tube defects: Genetic causes and prevention
- 2009 HUMAN MUTATION
Novel Mutations in VANGL1 in Neural Tube Defects
- 2015 BIRTH DEFECTS RES A
Genetic Studies of ANKRD6 as a Molecular Switch Between Wnt Signaling Pathways in Human Neural Tube Defects
- 2011 HUMAN MOLECULAR GENETICS
Mutations in the planar cell polarity gene, Fuzzy, are associated with neural tube defects in humans
- 2011 CLINICAL GENETICS
Contribution of VANGL2 mutations to isolated neural tube defects
