Abstract
Neural tube defects (NTDs) constitute the second most frequent cause of human congenital abnormalities. Complex multigenetic causes have been suggested to contribute to NTDs. The planar cell polarity (PCP) pathway plays a critical role in neural tube closure in model organisms and in human. Knockout of Dact1 (Dapper, Frodo) leads to deregulated PCP signaling with defective neural tube in mice. Here, we report that five missense heterozygote mutations of the DACT1 gene are specifically identified in 167 stillborn or miscarried Han Chinese fetuses with neural tube defects. Our biochemical analyses revealed that among the five mutations, N356K and R45W show loss-of-function or reduced activities in inducing Dishevelled2 (DVL2) degradation and inhibiting jun-N-terminal kinase (JNK) phosphorylation, implicating mutated DACT1 as a risk factor for human NTDs. Our findings, together with early reports, suggest that rare mutations of the PCP-related genes may constitute a great contribution to human NTDs.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
