title: POLG mutations associated with remitting/relapsing neurological events.
abstract: Recent experimental data underline the relationship between mitochondria and immune function. Clinical reports of patients presenting with mitochondrial dysfunction associated with dysimmune responses in the central nervous system reinforce this new concept. We describe the first case of a woman presenting with symptoms related to a novel compound heterozygous mutation of the mitochondrial polymerase γ (POLG) gene, associated with neurological events suggestive of a demyelinating process. Clinical examination revealed bilateral ptosis, progressive external ophthalmoplegia and axonal sensitive polyneuropathy suggestive of a mitochondrial disease. In line with this, muscle biopsy showed ragged red fibers, and sequencing of POLG revealed two heterozygous mutations. In addition, the patient exhibited relapsing neurological symptoms, and cerebral and spinal MRI mimicking multiple sclerosis. This patient stresses the relationship between mitochondrial dysfunction and inflammation. Recent studies suggest that targeting mitochondrial dysfunction could provide benefits in treating some inflammatory diseases.
authors.affiliation: Département de Neurologie, Hôpital Pitié-Salpêtrière, AP-HP, 47-83 boulevard de l'Hôpital, 75013 Paris, France; Université Pierre et Marie Curie (Paris VI), Paris, France. Electronic address: bertrand.degos@psl.aphp.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Degos
authors.affiliation: Centre de référence de pathologie neuromusculaire Paris-Est, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France; Institut de Myologie, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Laforêt
authors.affiliation: Laboratoire de Biochimie Métabolique, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Jardel
authors.affiliation: Département de Neurologie, Hôpital Pitié-Salpêtrière, AP-HP, 47-83 boulevard de l'Hôpital, 75013 Paris, France; Université Pierre et Marie Curie (Paris VI), Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sedel
authors.affiliation: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France.
authors.forename: Murielle
authors.initials: M
authors.lastname: Jossay-Winter
authors.affiliation: Département de Neurologie, Hôpital Pitié-Salpêtrière, AP-HP, 47-83 boulevard de l'Hôpital, 75013 Paris, France; Institut de Myologie, Unité de Morphologie Neuromusculaire, Inserm UMRS 974, CNRS UMR 7215, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Norma B
authors.initials: NB
authors.lastname: Romero
authors.affiliation: Département de Neurologie, Hôpital Pitié-Salpêtrière, AP-HP, 47-83 boulevard de l'Hôpital, 75013 Paris, France; Université Pierre et Marie Curie (Paris VI), Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lyon-Caen
authors.affiliation: Service de Neurologie et Faculté de Médecine, Université Champagne-Ardenne CHU de Reims, Reims, France; Laboratoire de psychopathologie et Neuropsychologie, EA2027 Université Paris, France.
authors.forename: Ayman
authors.initials: A
authors.lastname: Tourbah
mesh_terms: D000328:Adult; D017668:Age of Onset; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology*
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human
keywords: Immunology; Magnetic resonance imaging; Mitochondrial disorders; Multiple sclerosis; Myopathy