@article {Lefebvrejmedgenet-2017-104939, author = {Mathilde Lefebvre and Anne Dieux-Coeslier and Genevi{\`e}ve Baujat and Elise Schaefer and Saint-Onge Judith and Anne Bazin and Lucile Pinson and Tania Attie-Bitach and Clarisse Baumann and Melanie Fradin and Genevieve Pierquin and Sophie Julia and Chlo{\'e} Qu{\'e}lin and B{\'e}r{\'e}nice Doray and Sylvie Berg and Catherine Vincent-Delorme and Laetitia Lambert and Nadine Bachmann and Didier Lacombe and Bertrand Isidor and Nicole Laurent and Roume Joelle and Patricia Blanchet and Sylvie Odent and Dominique Kervran and Nathalie Leporrier and Carine Abel and Karine Segers and Fabienne Guiliano and Emmanuelle Ginglinger-Fabre and Angelo Selicorni and Alice Goldenberg and Salima El Chehadeh and Christine Francannet and Benedicte Demeer and Yannis Duffourd and Christel Thauvin-Robinet and Alain Verloes and Valerie Cormier-Daire and Jean Baptiste Riviere and Laurence Faivre and Julien Thevenon}, title = {Diagnostic strategy in segmentation defect of the vertebrae: a retrospective study of 73 patients}, elocation-id = {jmedgenet-2017-104939}, year = {2018}, doi = {10.1136/jmedgenet-2017-104939}, publisher = {BMJ Publishing Group Ltd}, 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.}, issn = {0022-2593}, URL = {https://jmg.bmj.com/content/early/2018/02/19/jmedgenet-2017-104939}, eprint = {https://jmg.bmj.com/content/early/2018/02/19/jmedgenet-2017-104939.full.pdf}, journal = {Journal of Medical Genetics} }