PT - JOURNAL ARTICLE AU - Mathilde Lefebvre AU - Anne Dieux-Coeslier AU - Geneviève Baujat AU - Elise Schaefer AU - Saint-Onge Judith AU - Anne Bazin AU - Lucile Pinson AU - Tania Attie-Bitach AU - Clarisse Baumann AU - Melanie Fradin AU - Genevieve Pierquin AU - Sophie Julia AU - Chloé Quélin AU - Bérénice Doray AU - Sylvie Berg AU - Catherine Vincent-Delorme AU - Laetitia Lambert AU - Nadine Bachmann AU - Didier Lacombe AU - Bertrand Isidor AU - Nicole Laurent AU - Roume Joelle AU - Patricia Blanchet AU - Sylvie Odent AU - Dominique Kervran AU - Nathalie Leporrier AU - Carine Abel AU - Karine Segers AU - Fabienne Guiliano AU - Emmanuelle Ginglinger-Fabre AU - Angelo Selicorni AU - Alice Goldenberg AU - Salima El Chehadeh AU - Christine Francannet AU - Benedicte Demeer AU - Yannis Duffourd AU - Christel Thauvin-Robinet AU - Alain Verloes AU - Valerie Cormier-Daire AU - Jean Baptiste Riviere AU - Laurence Faivre AU - Julien Thevenon TI - Diagnostic strategy in segmentation defect of the vertebrae: a retrospective study of 73 patients AID - 10.1136/jmedgenet-2017-104939 DP - 2018 Jun 01 TA - Journal of Medical Genetics PG - 422--429 VI - 55 IP - 6 4099 - http://jmg.bmj.com/content/55/6/422.2.short 4100 - http://jmg.bmj.com/content/55/6/422.2.full SO - J Med Genet2018 Jun 01; 55 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.