Abstract
Neural tube defect disorders are developmental diseases that originate from an incomplete closure of the neural tube during embryogenesis. Despite high prevalence—1 out of 3000 live births—their etiology is not yet established and both environmental and genetic factors have been proposed, with a heritability rate of about 60%. Studies in mouse models as well as in human have further suggested a multifactorial pattern of inheritance for neural tube defect disorders. Here, we report results obtained from clinical diagnosis and NGS analysis of a cohort composed of 52 patients. Using a candidate gene panel approach, we identified variants in known genes of planar cell polarity (PCP) pathway, although with higher prevalence than previously reported. Our study also reveals variants in novel genes such as FREM2 and DISP1. Altogether, these results confirm the implication of the PCP genes and involve the FRAS/FREM2 complex and Sonic Hedgehog signaling as novel components in the appearance of NTDs.
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Acknowledgements
We thank the Committee of Clinical and Translational Research (CORECT) of the University Hospital of Rennes for funding this work, the members of the National Reference Center for Spina Bifida of Rennes, Artem Kim for carefully reading this manuscript and the French Exome Project (FREX) for providing a control cohort.
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Supplementary material 1 Sanger electropherograms of the identified genetic variants. a patient, b control, f father, m mother (PDF 545 KB)
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Beaumont, M., Akloul, L., Carré, W. et al. Targeted panel sequencing establishes the implication of planar cell polarity pathway and involves new candidate genes in neural tube defect disorders. Hum Genet 138, 363–374 (2019). https://doi.org/10.1007/s00439-019-01993-y
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DOI: https://doi.org/10.1007/s00439-019-01993-y