title: Vestibular dysfunction in a Japanese patient with a mutation in the gene OPA1.
abstract: OPA1 mutations are known to cause autosomal dominant optic atrophy (ADOA), and some types of OPA1 mutations also cause auditory neuropathy. In the present study, we evaluated the vestibular dysfunction that accompanied auditory neuropathy in a patient with an OPA1 mutation. A caloric test failed to elicit nystagmus or dizziness in either ear. Vestibular evoked myogenic potentials (VEMPs) in the right ear were characterized by a normal biphasic waveform. In contrast, no VEMPs were evoked in the left ear. Model building suggested that the OPA1 mutation, p.R445H, indirectly distorts the catalytic structure of the GTPase reaction center and decreases GTPase activity. The patient complained of instability while walking or moving but thought these symptoms were caused by visual dysfunction. This is the first report of a detailed evaluation of vestibular dysfunction in a patient with an OPA1 mutation. This case suggests that vestibular dysfunction may be involved in motor instability in patients with an OPA1 mutation, even when patients do not complain of vestibular symptoms. Based on this case, we suggest that vestibular evaluation should be performed in auditory neuropathy patients carrying an OPA1 mutation, even if the patients are free of symptoms of vestibular dysfunction.
authors.affiliation: Department of Otolaryngology, Keio University School of Medicine, Tokyo, Japan. tari@mbf.ocn.ne.jp
authors.forename: Kunio
authors.initials: K
authors.lastname: Mizutari
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kaneko
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yagi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Namba
authors.forename: Satoko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Kaga
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D001301:Audiometry, Pure-Tone / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007564:Japan; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D010525:Peripheral Nerves / Q000473:pathology; D015837:Vestibular Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human