title: EFTUD2 haploinsufficiency leads to syndromic oesophageal atresia.
abstract: 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.
authors.affiliation: Unité INSERM U781, Faculté Paris-Descartes, Institut IMAGINE, Paris, France.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Gordon
authors.forename: Florence
authors.initials: F
authors.lastname: Petit
authors.forename: Myriam
authors.initials: M
authors.lastname: Oufadem
authors.forename: Charles
authors.initials: C
authors.lastname: Decaestecker
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Jourdain
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.forename: Valérie
authors.initials: V
authors.lastname: Malan
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Alessandri
authors.forename: Geneviève
authors.initials: G
authors.lastname: Baujat
authors.forename: Clarisse
authors.initials: C
authors.lastname: Baumann
authors.forename: Odile
authors.initials: O
authors.lastname: Boute-Benejean
authors.forename: Roseline
authors.initials: R
authors.lastname: Caumes
authors.forename: Bruno
authors.initials: B
authors.lastname: Delobel
authors.forename: Klaus
authors.initials: K
authors.lastname: Dieterich
authors.forename: Dominique
authors.initials: D
authors.lastname: Gaillard
authors.forename: Marie
authors.initials: M
authors.lastname: Gonzales
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Fabienne
authors.initials: F
authors.lastname: Escande
authors.forename: Sylvie
authors.initials: S
authors.lastname: Manouvrier-Hanu
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marlin
authors.forename: Michèle
authors.initials: M
authors.lastname: Mathieu-Dramard
authors.forename: Sarju G
authors.initials: SG
authors.lastname: Mehta
authors.forename: Ingrid
authors.initials: I
authors.lastname: Simonic
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Nicole
authors.initials: N
authors.lastname: Porchet
authors.forename: Loïc
authors.initials: L
authors.lastname: de Pontual
authors.forename: Sabine
authors.initials: S
authors.lastname: Sarnacki
authors.forename: Tania
authors.initials: T
authors.lastname: Attie-Bitach
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D055028:Comparative Genomic Hybridization; D004933:Esophageal Atresia / Q000235:genetics*; D019066:Facies; D005260:Female; D057895:Haploinsufficiency; D006801:Humans; D007223:Infant; D008297:Male; D010445:Peptide Elongation Factors / Q000235:genetics*; D010641:Phenotype; D017415:Ribonucleoprotein, U5 Small Nuclear; D013577:Syndrome
chemical_list: C581608:EFTUD2 protein, human; D010445:Peptide Elongation Factors; D017415:Ribonucleoprotein, U5 Small Nuclear