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Diagnostic strategy in segmentation defect of the vertebrae: a retrospective study of 73 patients

Mathilde Lefebvre 1, 2, 3 Anne Dieux-Coeslier 4 Geneviève Baujat 5 Elise Schaefer 6 Saint-Onge Judith 3 Anne Bazin Lucile Pinson 7 Tania Attié-Bitach 5 Clarisse Baumann 8 Mélanie Fradin 9 Geneviève Pierquin 10 Sophie Julia 11 Chloé Quélin 9 Bérénice Doray Sylvie Berg Catherine Vincent-Delorme 12 Laetitia Lambert 13 Nadine Bachmann Didier Lacombe 14 Bertrand Isidor 15 Nicole Laurent 16 Roume Joelle Patricia Blanchet 17 Sylvie Odent 18 Dominique Kervran Nathalie Leporrier 19 Carine Abel Karine Segers Fabienne Guiliano Emmanuelle Ginglinger-Fabre Angelo Selicorni Alice Goldenberg Salima El Chehadeh Christine Francannet 20 Bénédicte Demeer 21 Yannis Duffourd 3 Christel Thauvin-Robinet 1, 2, 3 Alain Verloes 22 Valérie Cormier-Daire 4 Jean Baptiste Riviere 3 Laurence Faivre 1, 2, 3 Julien Thevenon 23, 1, 2, 3
Abstract : Background Segmentation defects of the vertebrae (SDV) are non-specific features found in various syndromes. The molecular bases of SDV are not fully elucidated due to the wide range of phenotypes and classification issues. The genes involved are in the Notch signalling pathway, which is a key system in somitogenesis. Here we report on mutations identified in a diagnosis cohort of SDV. We focused on spondylocostal dysostosis (SCD) and the phenotype of these patients in order to establish a diagnostic strategy when confronted with SDV.Patients and methods We used DNA samples from a cohort of 73 patients and performed targeted sequencing of the five known SCD-causing genes (DLL3, MESP2, LFNG, HES7 and TBX6) in the first 48 patients and whole-exome sequencing (WES) in 28 relevant patients.Results Ten diagnoses, including four biallelic variants in TBX6, two biallelic variants in LFNG and DLL3, and one in MESP2 and HES7, were made with the gene panel, and two diagnoses, including biallelic variants in FLNB and one variant in MEOX1, were made by WES. The diagnostic yield of the gene panel was 10/73 (13.7%) in the global cohort but 8/10 (80%) in the subgroup meeting the SCD criteria; the diagnostic yield of WES was 2/28 (8%).Conclusion After negative array CGH, targeted sequencing of the five known SCD genes should only be performed in patients who meet the diagnostic criteria of SCD. The low proportion of candidate genes identified by WES in our cohort suggests the need to consider more complex genetic architectures in cases of SDV.
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-02012240
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : vendredi 8 février 2019 - 15:42:53
Dernière modification le : vendredi 15 mai 2020 - 12:22:05

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Mathilde Lefebvre, Anne Dieux-Coeslier, Geneviève Baujat, Elise Schaefer, Saint-Onge Judith, et al.. Diagnostic strategy in segmentation defect of the vertebrae: a retrospective study of 73 patients. Journal of Medical Genetics, BMJ Publishing Group, 2018, 55 (6), pp.422-429. ⟨10.1136/jmedgenet-2017-104939⟩. ⟨hal-02012240⟩

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