Role of the planar cell polarity gene Protein tyrosine kinase 7 in neural tube defects in humans

Mingqin Wang, Patrizia De Marco, Elisa Merello, Pierre Drapeau, Valeria Capra, Zoha Kibar

Research output: Contribution to journalArticlepeer-review


Background: Neural tube defects (NTDs) are among the most common congenital defects affecting approximately 1 in 1000 live births in North America. Their etiology is complex including environmental and genetic factors. Defects in the planar cell polarity (PCP) signaling pathway have been strongly associated with NTDs in animal models and human cohorts. Protein tyrosine kinase 7 (Ptk7) was shown to cause a very severe form of NTDs called craniorachischisis in a mouse model and genetically interacts with a core PCP member Vangl2 where double heterozygotes suffer from spina bifida. In this study, we examined the role of PTK7 in human NTDs to determine whether variants at this gene predispose to these defects. Methods: We sequenced the coding region and the exon-intron junctions of PTK7 in a cohort of 473 patients affected with various forms of open and closed NTDs. Novel and rare variants(<1%) were genotyped in a cohort of 473 individuals. Their pathogenic effect was predicted in silico and functionally in an overexpression assay in a well-established zebrafish model. Results: We identified in our cohort 6 rare variants, 3 of which were absent in public databases. One variant, p.Gly348Ser, acted as a hypermorph when overexpressed in the zebrafish model. Conclusion: We detected potentially pathogenic PTK7 variants in 1.1% of our NTD cohort. Our findings implicate PTK7 as a risk factor for NTDs and provide additional evidence for a pathogenic role of PCP signaling in these malformations. Birth Defects Research (Part A), 103:1021-1027, 2015.

Original languageEnglish
Pages (from-to)1021-1027
Number of pages7
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Issue number12
Publication statusPublished - Dec 1 2015


  • Neural tube defects
  • Planar cell polarity pathway
  • PTK7
  • Sequencing analysis
  • Zebrafish model

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Developmental Biology


Dive into the research topics of 'Role of the planar cell polarity gene Protein tyrosine kinase 7 in neural tube defects in humans'. Together they form a unique fingerprint.

Cite this