title: Phenotypic diversity associated with the MT-TV gene m.1644G>A mutation, a matter of quantity.
abstract: We describe four patients from three independent families with the m.1644G>A in the MT-TV gene, previously reported without demonstration of its deleterious impact. Very high mutation proportion co-segregated with cytochrome oxidase defect in single muscle fibers and respiratory defect in cybrids as shown by spectrophotometric assays and polarography. The mutation appeared to have a very steep threshold effect with asymptomatic life up to 70% mutation proportion, progressive encephalopathy above 80% and severe Leigh-like syndrome above 95% mutation. One patient did not fit within that frame but presented with characteristics suggesting the presence of an additional disease.
authors.affiliation: AP-HP, Hôpital de La Salpêtrière, Fédération de Neurologie, Paris F-75651, France.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Fraidakis
authors.affiliation: AP-HP, Hôpital de La Salpêtrière, Service de Biochimie Métabolique et Centre de Génétique moléculaire et chromosomique, Paris F-75651, France; INSERM, UMRS 1016, Institut Cochin, Paris F-75014, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Jardel
authors.affiliation: CHU, Service de Biochimie, Pôle de biologie, Côte de Nâcre, 14033 Caen cedex 09, France; Normandie Université UNICAEN, EA 4650, 14032 Caen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Allouche
authors.affiliation: Inserm U974, Institut de Myologie, Hôpital de La Salpêtrière, Paris F-75654, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Nelson
authors.affiliation: INSERM, UMRS 1016, Institut Cochin, Paris F-75014, France; AP/HP, Hôpital Ambroise Paré, Service d'explorations fonctionnelles, Boulogne-Billancourt F-92100, France; Université Versailles-Saint-Quentin en Yvelines, F-78180, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Auré
authors.affiliation: AP-HP, Hôpital de Bicêtre, Service de Biochimie, Le Kremlin-Bicêtre, F-94275, France.
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Slama
authors.affiliation: AP-HP, Hôpital de La Salpêtrière, Service de Biochimie Métabolique et Centre de Génétique moléculaire et chromosomique, Paris F-75651, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lemière
authors.affiliation: CHG Service de Neurologie, Alençon F-61000, France.
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Thenint
authors.affiliation: CHU, Hôpital la Cavale Blanche, Brest F-29200, France.
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Hamon
authors.affiliation: Service de Neurologie, Hôpital d'Instruction des Armées, Brest 29200, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zagnoli
authors.affiliation: AP-HP, Hôpital de La Salpêtrière, Centre de Référence des Déficiences Intellectuelles de Causes Rares, Groupe de Recherche Clinique (GRC) 'déficience intellectuelle et autisme', Paris F-75651, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Heron
authors.affiliation: AP-HP, Hôpital de La Salpêtrière, Fédération de Neurologie, Paris F-75651, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sedel
authors.affiliation: AP-HP, Hôpital de La Salpêtrière, Service de Biochimie Métabolique et Centre de Génétique moléculaire et chromosomique, Paris F-75651, France; INSERM, UMRS 1016, Institut Cochin, Paris F-75014, France; CNRS, UMR 8104, Institut Cochin, Paris F-75014, France; Université René Descartes-Paris 5, Paris F-75014, France. Electronic address: anne.lombes@inserm.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Lombès
mesh_terms: D050259:Genes, Mitochondrial; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology*; D017354:Point Mutation; D011048:Polarography; D040641:Quantitative Trait Loci; D012366:RNA, Transfer, Val / Q000235:genetics*; D013057:Spectrum Analysis
chemical_list: D012366:RNA, Transfer, Val
keywords: Clinical diagnosis; Heteroplasmy; Mitochondrial DNA; Mitochondrial diseases