title: Behr's Syndrome is Typically Associated with Disturbed Mitochondrial Translation and Mutations in theC12orf65Gene.
abstract: BACKGROUND
  Behr's syndrome is a classical phenotypic description of childhood-onset optic atrophy combined with various neurological symptoms, including ophthalmoparesis, nystagmus, spastic paraparesis, ataxia, peripheral neuropathy and learning difficulties.
  
  
  OBJECTIVE
  Here we describe 4 patients with the classical Behr's syndrome phenotype from 3 unrelated families who carry homozygous nonsense mutations in theC12orf65gene encoding a protein involved in mitochondrial translation.
  
  
  METHODS
  Whole exome sequencing was performed in genomic DNA and oxygen consumption was measured in patient cell lines.
  
  
  RESULTS
  We detected 2 different homozygousC12orf65nonsense mutations in 4 patients with a homogeneous clinical presentation matching the historical description of Behr's syndrome. The first symptom in all patients was childhood-onset optic atrophy, followed by spastic paraparesis, distal weakness, motor neuropathy and ophthalmoparesis.
  
  
  CONCLUSIONS
  We think thatC12orf65mutations are more frequent than previously suggested and screening of this gene should be considered not only in patients with mitochondrial respiratory chain deficiencies, but also in inherited peripheral neuropathies, spastic paraplegias and ataxias, especially with pre-existing optic atrophy.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Pyle
authors.affiliation: Department of Pediatric Neurology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Trust, UK.
authors.forename: Venkateswaran
authors.initials: V
authors.lastname: Ramesh
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Bartsakoulia
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Veronika
authors.initials: V
authors.lastname: Boczonadi
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Aurora
authors.initials: A
authors.lastname: Gomez-Duran
authors.affiliation: Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Agnes
authors.initials: A
authors.lastname: Herczegfalvi
authors.affiliation: Wellcome Trust Mitochondrial Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Blakely
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Tania
authors.initials: T
authors.lastname: Smertenko
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Duff
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Gail
authors.initials: G
authors.lastname: Eglon
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: David
authors.initials: D
authors.lastname: Moore
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Yu-Wai-Man
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Douroudis
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Mauro
authors.initials: M
authors.lastname: Santibanez-Koref
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Griffin
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.affiliation: Department of Molecular Genetics and Diagnostics, NIEH, Budapest, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Karcagi
authors.affiliation: Wellcome Trust Mitochondrial Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
keywords: Behr’s syndrome; ataxia; mitochondrial translation; optic atrophy; peripheral neuropathy; spastic paraplegia