Targeted panel sequencing establishes the implication of planar cell polarity pathway and involves new candidate genes in neural tube defect disorders

Marie Beaumont 1 Linda Akloul 1 Wilfrid Carré 2, 1 Chloé Quélin 1 Hubert Journel 3 Laurent Pasquier 1 Mélanie Fradin 1 Sylvie Odent 1, 2 Houda Hamdi-Roze 1 Erwan Watrin 2 Valérie Dupé 2 Christèle Dubourg 2, 1 Véronique David 2, 1
1 CHU Pontchaillou [Rennes]
2 IGDR - Institut de Génétique et Développement de Rennes
3 Centre Hospitalier Bretagne Atlantique [Vannes]
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.
Document type :
Journal articles
Complete list of metadatas
https://hal-univ-rennes1.archives-ouvertes.fr/hal-02119226
Contributor : Xavier Chard-Hutchinson <>
Submitted on : Friday, May 3, 2019 - 4:22:24 PM
Last modification on : Friday, June 14, 2019 - 3:32:47 PM

Identifiers

Collections

UNIV-RENNES1 | IGDR | BIOSIT | UR1-UFR-SVE | UNIV-RENNES

Citation

Marie Beaumont, Linda Akloul, Wilfrid Carré, Chloé Quélin, Hubert Journel, et al.. Targeted panel sequencing establishes the implication of planar cell polarity pathway and involves new candidate genes in neural tube defect disorders. Human Genetics, Springer Verlag, 2019, 138 (4), pp.363-374. ⟨10.1007/s00439-019-01993-y⟩. ⟨hal-02119226⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

12