RT Journal Article SR Electronic T1 EFTUD2 haploinsufficiency leads to syndromic oesophageal atresia JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 737 OP 746 DO 10.1136/jmedgenet-2012-101173 VO 49 IS 12 A1 Christopher T Gordon A1 Florence Petit A1 Myriam Oufadem A1 Charles Decaestecker A1 Anne-Sophie Jourdain A1 Joris Andrieux A1 Valérie Malan A1 Jean-Luc Alessandri A1 Geneviève Baujat A1 Clarisse Baumann A1 Odile Boute-Benejean A1 Roseline Caumes A1 Bruno Delobel A1 Klaus Dieterich A1 Dominique Gaillard A1 Marie Gonzales A1 Didier Lacombe A1 Fabienne Escande A1 Sylvie Manouvrier-Hanu A1 Sandrine Marlin A1 Michèle Mathieu-Dramard A1 Sarju G. Mehta A1 Ingrid Simonic A1 Arnold Munnich A1 Michel Vekemans A1 Nicole Porchet A1 Loïc de Pontual A1 Sabine Sarnacki A1 Tania Attie-Bitach A1 Stanislas Lyonnet A1 Muriel Holder-Espinasse A1 Jeanne Amiel YR 2012 UL http://jmg.bmj.com/content/49/12/737.abstract AB Background: Oesophageal atresia (OA) and mandibulofacial dysostosis (MFD) are two congenital malformations for which the molecular bases of syndromic forms are being identified at a rapid rate. In particular, the EFTUD2 gene encoding a protein of the spliceosome complex has been found mutated in patients with MFD and microcephaly (MIM610536). Until now, no syndrome featuring both MFD and OA has been clearly delineated. Results: We report on 10 cases presenting with MFD, eight of whom had OA, either due to de novo 17q21.31 deletions encompassing EFTUD2 and neighbouring genes or de novo heterozygous EFTUD2 loss-of-function mutations. No EFTUD2 deletions or mutations were found in a series of patients with isolated OA or isolated oculoauriculovertebral spectrum (OAVS). Conclusions: These data exclude a contiguous gene syndrome for the association of MFD and OA, broaden the spectrum of clinical features ascribed to EFTUD2 haploinsufficiency, define a novel syndromic OA entity, and emphasise the necessity of mRNA maturation through the spliceosome complex for global growth and within specific regions of the embryo during development. Importantly, the majority of patients reported here with EFTUD2 lesions were previously diagnosed with Feingold or CHARGE syndromes or presented with OAVS plus OA, highlighting the variability of expression and the wide range of differential diagnoses.