Rare missense variants in DVL1, one of the human counterparts of the Drosophila dishevelled gene, do not confer increased risk for neural tube defects

Elisa Merello, Zoha Kibar, Redouane Allache, Gianluca Piatelli, Armando Cama, Valeria Capra, Patrizia De Marco

Research output: Contribution to journalArticle

Abstract

Neural tube defects (NTDs) are severe malformations that arise when the neural tube fails to close during embryogenesis. The planar cell polarity pathway is involved in neural tube closure and has been implicated in the pathogenesis of NTDs both in animal models and human cohorts. Dishevelled (Dvl/Dsh) is a multi-module protein and a key regulator of both the canonical Wnt and the PCP pathway. In mouse, all Dvl1-/-; Dvl2-/- double mutants display craniorachischisis, a severe form of open NTDs. Recently, we have reported a possible role for rare variants of DVL2 as risk factors for NTDs. METHODS: In view of these data, we hypothesized that DVL1 mutations might increase the risk for NTDs in some cases. Resequencing of the DVL1 gene in a cohort of 473 NTDs patients and 150 ethnically matched controls was performed. Prediction of the downstream effects of the nonsynonymous variants was done using computational methods. RESULTS: We identified six missense variants that were absent in our ethnically matched controls group, and four of them (p.Arg153Cys; p.Glu544Arg; p.Arg568Trp; p.Val644Phe) were predicted to have a functional effect on protein structure by one or more bioinformatic programs. However, there was no difference in the overall rate of deleterious variants between the patients and controls (four in patients and three in controls; p=0.36). CONCLUSION: Our findings did not provide evidence for the implication of DVL1 in the pathogenesis of human NTDs. Birth Defects Research (Part A) 97:452-455, 2013.

Original languageEnglish
Pages (from-to)452-455
Number of pages4
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume97
Issue number7
DOIs
Publication statusPublished - Jul 2013

Keywords

  • Convergent extension
  • Dishevelled (DVL)
  • Neural tube defects (NTDs)
  • Planar cell polarity (PCP) pathway

ASJC Scopus subject areas

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

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