title: CHCHD10 variant p.(Gly66Val) causes axonal Charcot-Marie-Tooth disease.
abstract: OBJECTIVE
  We describe the phenotype consistent with axonal Charcot-Marie-Tooth disease type 2 (CMT2) in 4 families with a c.197G>T (p.(Gly66Val)) variant in CHCHD10.
  
  
  METHODS
  We sequenced the CHCHD10 gene in a cohort of 107 families with CMT2 of unknown etiology. The patients were characterized by clinical examination and electroneuromyography. Muscle MRI and biopsy of the muscle or nerve were performed in selected cases. Neuropathologic autopsy was performed in 1 case.
  
  
  RESULTS
  The c.197G>T variant in CHCHD10 was found in 6 families, 4 of which included multiple individuals available for detailed clinical study. Variants in this gene have recently been associated with amyotrophic lateral sclerosis-frontotemporal dementia, mitochondrial myopathy, or spinal muscular atrophy Jokela type (SMAJ), but not with CMT2. Our patients had a late-onset distal axonal neuropathy with motor predominance, progressing to involve sensory nerves. Neurophysiologic and neuropathologic studies confirmed the diagnosis of sensorimotor axonal neuropathy with no loss of anterior horn neurons. Muscle biopsies showed occasional cytochrome c oxidase-negative fibers, combined with small amounts of mitochondrial DNA deletions.
  
  
  CONCLUSIONS
  CHCHD10 c.197G>T (p.(Gly66Val)) is a cause of sensorimotor axonal neuropathy. This gene should be considered in patients presenting with a pure CMT2 phenotype, particularly when motor symptoms predominate.
authors.affiliation: Research Programs Unit (M.A., E.Y., M.S., H.T.), Molecular Neurology, University of Helsinki; Clinical Neurosciences, Neurology (M.A., S.K.-E.), University of Helsinki and Helsinki University Hospital; Department of Pathology (A.P.), HUSLAB & University of Helsinki; Department of Clinical Neurophysiology (J.P.T.), Medical Imaging Center, Helsinki University Hospital; and Department of Medical Genetics (H.T.), Haartman Institute, University of Helsinki, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Auranen
authors.affiliation: Research Programs Unit (M.A., E.Y., M.S., H.T.), Molecular Neurology, University of Helsinki; Clinical Neurosciences, Neurology (M.A., S.K.-E.), University of Helsinki and Helsinki University Hospital; Department of Pathology (A.P.), HUSLAB & University of Helsinki; Department of Clinical Neurophysiology (J.P.T.), Medical Imaging Center, Helsinki University Hospital; and Department of Medical Genetics (H.T.), Haartman Institute, University of Helsinki, Finland.
authors.forename: Emil
authors.initials: E
authors.lastname: Ylikallio
authors.affiliation: Research Programs Unit (M.A., E.Y., M.S., H.T.), Molecular Neurology, University of Helsinki; Clinical Neurosciences, Neurology (M.A., S.K.-E.), University of Helsinki and Helsinki University Hospital; Department of Pathology (A.P.), HUSLAB & University of Helsinki; Department of Clinical Neurophysiology (J.P.T.), Medical Imaging Center, Helsinki University Hospital; and Department of Medical Genetics (H.T.), Haartman Institute, University of Helsinki, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Shcherbii
authors.affiliation: Research Programs Unit (M.A., E.Y., M.S., H.T.), Molecular Neurology, University of Helsinki; Clinical Neurosciences, Neurology (M.A., S.K.-E.), University of Helsinki and Helsinki University Hospital; Department of Pathology (A.P.), HUSLAB & University of Helsinki; Department of Clinical Neurophysiology (J.P.T.), Medical Imaging Center, Helsinki University Hospital; and Department of Medical Genetics (H.T.), Haartman Institute, University of Helsinki, Finland.
authors.forename: Anders
authors.initials: A
authors.lastname: Paetau
authors.affiliation: Research Programs Unit (M.A., E.Y., M.S., H.T.), Molecular Neurology, University of Helsinki; Clinical Neurosciences, Neurology (M.A., S.K.-E.), University of Helsinki and Helsinki University Hospital; Department of Pathology (A.P.), HUSLAB & University of Helsinki; Department of Clinical Neurophysiology (J.P.T.), Medical Imaging Center, Helsinki University Hospital; and Department of Medical Genetics (H.T.), Haartman Institute, University of Helsinki, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Kiuru-Enari
authors.affiliation: Research Programs Unit (M.A., E.Y., M.S., H.T.), Molecular Neurology, University of Helsinki; Clinical Neurosciences, Neurology (M.A., S.K.-E.), University of Helsinki and Helsinki University Hospital; Department of Pathology (A.P.), HUSLAB & University of Helsinki; Department of Clinical Neurophysiology (J.P.T.), Medical Imaging Center, Helsinki University Hospital; and Department of Medical Genetics (H.T.), Haartman Institute, University of Helsinki, Finland.
authors.forename: Jussi P
authors.initials: JP
authors.lastname: Toppila
authors.affiliation: Research Programs Unit (M.A., E.Y., M.S., H.T.), Molecular Neurology, University of Helsinki; Clinical Neurosciences, Neurology (M.A., S.K.-E.), University of Helsinki and Helsinki University Hospital; Department of Pathology (A.P.), HUSLAB & University of Helsinki; Department of Clinical Neurophysiology (J.P.T.), Medical Imaging Center, Helsinki University Hospital; and Department of Medical Genetics (H.T.), Haartman Institute, University of Helsinki, Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Tyynismaa