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Updated: May 27, 2026

Evaluation of Planar-Cell-Polarity Phenotypes in Ciliopathy Mouse Mutant Cochlea
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Published on: February 21, 2016

Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect

Alexis Robinson1, Sarah Escuin, Kit Doudney

  • 1UCL Institute of Child Health, London WC1N 1EH, United Kingdom.

Human Mutation
|November 19, 2011
PubMed

Insights

Craniorachischisis, a severe neural tube defect, may be caused by mutations in CELSR1 and SCRIB genes. These mutations disrupt planar cell polarity protein trafficking to the cell membrane, similar to mouse models.

Area of Science:

  • Developmental Biology
  • Genetics
  • Cell Biology

Background:

  • Craniorachischisis (CRN) is a severe neural tube defect (NTD) with an unknown genetic cause in humans.
  • Mouse models implicate planar cell polarity (PCP) pathway genes in CRN.
  • Previous studies did not find mutations in VANGL1 and VANGL2 in human CRN patients.

Purpose of the Study:

  • To investigate the role of additional PCP genes (CELSR1, PRICKLE1, PTK7, SCRIB) in human CRN.
  • To identify causative mutations and understand their functional consequences in CRN.

Main Methods:

  • Sequencing of CELSR1, PRICKLE1, PTK7, and SCRIB genes in 36 CRN patients.
  • Analysis of protein-protein interactions for identified variants.
  • Assessment of subcellular protein localization of variants, including comparison with mouse models (Celsr1 and Scrib mutants).

Main Results:

  • Eight potentially causative mutations were identified in CELSR1 and SCRIB genes.
  • Five of 36 patients with variants showed significantly altered subcellular localization of PCP proteins, with reduced plasma membrane trafficking.
  • These localization defects mirrored those observed in Celsr1 and Scrib mouse mutants.

Conclusions:

  • Missense variants in CELSR1 and SCRIB are potential causes of CRN in humans.
  • Defective trafficking of PCP proteins to the plasma membrane is a likely pathogenic mechanism for CRN.

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