title: Leber hereditary optic neuropathy due to a new ND1 mutation.
abstract: We report a proband with Leber hereditary optic neuropathy (LHON), in whom we have identified a novel homoplasmic m.3,395A>G mutation in the ND1 gene. The mutation alters a highly conserved amino acid in codon 30 which previously has been associated with LHON and leads to a severe selective complex I deficiency. By providing further evidence for pathogenicity we conclude that m.3,395A>G is pathogenic. High definition optical coherence tomography of the retina and peripapillary retinal nerve fiber layer (pRNFL) confirms recent reports that retinal ganglion cell loss precedes axonal loss in LHON and is present in the early stage of the disease. Furthermore, evaluation of two unaffected mutation carriers disclosed asymptomatic borderline ganglion cell loss and thin pRNFL in one.
authors.affiliation: a Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.|b Copenhagen Neuromuscular Center , Department of Neurology , Rigshospitalet, Copenhagen , Denmark.
authors.forename: Patrick
authors.initials: P
authors.lastname: Soldath
authors.affiliation: a Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.|c Department of Ophthalmology , Rigshospitalet, Copenhagen , Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Wegener
authors.affiliation: c Department of Ophthalmology , Rigshospitalet, Copenhagen , Denmark.
authors.forename: Birgit
authors.initials: B
authors.lastname: Sander
authors.affiliation: a Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.|c Department of Ophthalmology , Rigshospitalet, Copenhagen , Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
authors.affiliation: d Department of Clinical Genetics , Rigshospitalet, Copenhagen , Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Duno
authors.affiliation: d Department of Clinical Genetics , Rigshospitalet, Copenhagen , Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Wibrand
authors.affiliation: a Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.|b Copenhagen Neuromuscular Center , Department of Neurology , Rigshospitalet, Copenhagen , Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Vissing
mesh_terms: D000293:Adolescent; D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D009412:Nerve Fibers / Q000473:pathology; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012165:Retinal Ganglion Cells / Q000473:pathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human
keywords: Complex I deficiency; LHON; ND1 gene; leber hereditary optic neuropathy; mitochondrial DNA; optical coherence tomography; retinal ganglion cell; retinal nerve fiber layer