title: Novel de novo EEF1A2 missense mutations causing epilepsy and intellectual disability.
abstract: BACKGROUND
  Exome sequencing has led to the discovery of mutations in novel causative genes for epilepsy. One such gene is EEF1A2, encoding a neuromuscular specific translation elongation factor, which has been found to be mutated de novo in five cases of severe epilepsy. We now report on a further seven cases, each with a different mutation, of which five are newly described.
  
  
  METHODS
  New cases were identified and sequenced through the Deciphering Developmental Disabilities project, via direct contact with neurologists or geneticists, or recruited via our website.
  
  
  RESULTS
  All the mutations cause epilepsy and intellectual disability, but with a much wider range of severity than previously identified. All new cases share specific subtle facial dysmorphic features. Each mutation occurs at an evolutionarily highly conserved amino acid position indicating strong structural or functional selective pressure.
  
  
  CONCLUSIONS
  EEF1A2 should be considered as a causative gene not only in cases of epileptic encephalopathy but also in children with less severe epilepsy and intellectual disability. The emergence of a possible discernible phenotype, a broad nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth may help in identifying patients with mutations in EEF1A2.
authors.affiliation: South East of Scotland Clinical Genetics ServiceCrewe RoadEdinburghUK; Centre for Genomic & Experimental MedicineMRC Institute of Genetics and Molecular MedicineUniversity of EdinburghWestern General HospitalCrewe RoadEdinburghEH4 2XUUK; Muir Maxwell Epilepsy CentreUniversity of Edinburgh20 Sylvan PlaceEdinburghEH9 1UWUK; Paediatric NeurosciencesRoyal Hospital for Sick ChildrenSciennes RoadEdinburghEH9 1LFUK.
authors.forename: Wayne W K
authors.initials: WW
authors.lastname: Lam
authors.affiliation: Epilepsy Center Departments of Pediatrics and Neurology Ann & Robert H. Lurie Children's Hospital of Chicago Northwestern University Feinberg School of Medicine 225 E Chicago Ave Box #29 Chicago Illinois 60611.
authors.forename: John J
authors.initials: JJ
authors.lastname: Millichap
authors.affiliation: Centre for Genomic & Experimental MedicineMRC Institute of Genetics and Molecular MedicineUniversity of EdinburghWestern General HospitalCrewe RoadEdinburghEH4 2XUUK; MRC Human Genetics UnitMRC Institute of Genetics and Molecular MedicineUniversity of EdinburghWestern General HospitalCrewe RoadEdinburghEH4 2XUUK.
authors.forename: Dinesh C
authors.initials: DC
authors.lastname: Soares
authors.affiliation: Muir Maxwell Epilepsy CentreUniversity of Edinburgh20 Sylvan PlaceEdinburghEH9 1UWUK; Paediatric NeurosciencesRoyal Hospital for Sick ChildrenSciennes RoadEdinburghEH9 1LFUK; Child Life and HealthUniversity of Edinburgh20 Sylvan PlaceEdinburghEH9 1UWUK.
authors.forename: Richard
authors.initials: R
authors.lastname: Chin
authors.affiliation: Paediatric Neurosciences Royal Hospital for Sick Children Sciennes Road Edinburgh EH9 1LF UK.
authors.forename: Ailsa
authors.initials: A
authors.lastname: McLellan
authors.affiliation: Paediatric NeurosciencesRoyal Hospital for Sick ChildrenSciennes RoadEdinburghEH9 1LFUK; MRC Human Genetics UnitMRC Institute of Genetics and Molecular MedicineUniversity of EdinburghWestern General HospitalCrewe RoadEdinburghEH4 2XUUK.
authors.forename: David R
authors.initials: DR
authors.lastname: FitzPatrick
authors.affiliation: South West Thames Regional Genetics Service St George's Hospital Tooting London UK.
authors.forename: Frances
authors.initials: F
authors.lastname: Elmslie
authors.affiliation: Department of Clinical Genetics Great Ormond Street Hospital Great Ormond Street London UK.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Lees
authors.affiliation: Division of Medical Genetics Arkansas Children's Hospital Little Rock Arkansas.
authors.forename: G Bradley
authors.initials: GB
authors.lastname: Schaefer
authors.affiliation: Centre for Genomic & Experimental MedicineMRC Institute of Genetics and Molecular MedicineUniversity of EdinburghWestern General HospitalCrewe RoadEdinburghEH4 2XUUK; Muir Maxwell Epilepsy CentreUniversity of Edinburgh20 Sylvan PlaceEdinburghEH9 1UWUK.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Abbott
keywords: Autism; EEF1A2; epilepsy; intellectual disability; translation elongation