RT Journal Article SR Electronic T1 Diagnostic strategy in segmentation defect of the vertebrae: a retrospective study of 73 patients JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP jmedgenet-2017-104939 DO 10.1136/jmedgenet-2017-104939 A1 Mathilde Lefebvre A1 Anne Dieux-Coeslier A1 Geneviève Baujat A1 Elise Schaefer A1 Saint-Onge Judith A1 Anne Bazin A1 Lucile Pinson A1 Tania Attie-Bitach A1 Clarisse Baumann A1 Melanie Fradin A1 Genevieve Pierquin A1 Sophie Julia A1 Chloé Quélin A1 Bérénice Doray A1 Sylvie Berg A1 Catherine Vincent-Delorme A1 Laetitia Lambert A1 Nadine Bachmann A1 Didier Lacombe A1 Bertrand Isidor A1 Nicole Laurent A1 Roume Joelle A1 Patricia Blanchet A1 Sylvie Odent A1 Dominique Kervran A1 Nathalie Leporrier A1 Carine Abel A1 Karine Segers A1 Fabienne Guiliano A1 Emmanuelle Ginglinger-Fabre A1 Angelo Selicorni A1 Alice Goldenberg A1 Salima El Chehadeh A1 Christine Francannet A1 Benedicte Demeer A1 Yannis Duffourd A1 Christel Thauvin-Robinet A1 Alain Verloes A1 Valerie Cormier-Daire A1 Jean Baptiste Riviere A1 Laurence Faivre A1 Julien Thevenon YR 2018 UL http://jmg.bmj.com/content/early/2018/02/19/jmedgenet-2017-104939.abstract AB 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.