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 422
OP 429
DO 10.1136/jmedgenet-2017-104939
VO 55
IS 6
A1 Lefebvre, Mathilde
A1 Dieux-Coeslier, Anne
A1 Baujat, Geneviève
A1 Schaefer, Elise
A1 Judith, Saint-Onge
A1 Bazin, Anne
A1 Pinson, Lucile
A1 Attie-Bitach, Tania
A1 Baumann, Clarisse
A1 Fradin, Melanie
A1 Pierquin, Genevieve
A1 Julia, Sophie
A1 Quélin, Chloé
A1 Doray, Bérénice
A1 Berg, Sylvie
A1 Vincent-Delorme, Catherine
A1 Lambert, Laetitia
A1 Bachmann, Nadine
A1 Lacombe, Didier
A1 Isidor, Bertrand
A1 Laurent, Nicole
A1 Joelle, Roume
A1 Blanchet, Patricia
A1 Odent, Sylvie
A1 Kervran, Dominique
A1 Leporrier, Nathalie
A1 Abel, Carine
A1 Segers, Karine
A1 Guiliano, Fabienne
A1 Ginglinger-Fabre, Emmanuelle
A1 Selicorni, Angelo
A1 Goldenberg, Alice
A1 El Chehadeh, Salima
A1 Francannet, Christine
A1 Demeer, Benedicte
A1 Duffourd, Yannis
A1 Thauvin-Robinet, Christel
A1 Verloes, Alain
A1 Cormier-Daire, Valerie
A1 Riviere, Jean Baptiste
A1 Faivre, Laurence
A1 Thevenon, Julien
YR 2018
UL http://jmg.bmj.com/content/55/6/422.2.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.