title: Late-onset spastic paraplegia type 10 (SPG10) family presenting with bulbar symptoms and fasciculations mimicking amyotrophic lateral sclerosis.
abstract: Pathogenic mutations in the KIF5A-SPG10 gene, encoding the kinesin HC5A, can be associated with autosomal dominant hereditary spastic paraplegia (ADHSP). It accounts for about 10% of the complicated forms of ADHSP. Peripheral neuropathy, distal upper limb amyotrophy, and cognitive decline are the most common additional clinical features. We examined a 66-year-old Japanese woman manifesting gait disturbance and spastic dysarthria for 6years with positive family history. She showed evidence of upper and lower motor neuron involvement and fasciculations, thus mimicking amyotrophic lateral sclerosis (ALS). Genetic analysis revealed a heterozygous variant in KIF5A (c.484C>T, p.Arg162Trp) in 2 symptomatic members. The mutation was also identified in 4 asymptomatic members, including 2 elderly members aged over 78years. Electromyography in the 2 symptomatic members revealed evidence of lower motor neuron involvement and fasciculation potentials in distal muscles. This report describes the first known Asian family with a KIF5A mutation and broadens the clinical and electrophysiological spectrum associated with KIF5A-SPG10 mutations. Given that our cases showed pseudobulbar palsy, fasciculation and altered penetrance, KIF5A-SPG10 might well be considered as a differential diagnosis of sporadic ALS.
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan; Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: seiji-kaji@hotmail.co.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kaji
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: tkawarai@tokushima-u.ac.jp.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Kawarai
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: ninigii@gmail.com.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Miyamoto
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: hnodera@tokushima-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nodera
authors.affiliation: Laboratorio di Neurogenetica, CERC-IRCCS Santa Lucia, Rome, Italy. Electronic address: l.pedace@hsantalucia.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pedace
authors.affiliation: Laboratorio di Neurogenetica, CERC-IRCCS Santa Lucia, Rome, Italy; Dipartimento di Scienze Chirurgiche e Biomolecolari, Università di Perugia, Perugia, Italy. Electronic address: a.orlacchio@hsantalucia.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Orlacchio
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: yizumi@tokushima-u.ac.jp.
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: ryosuket@kuhp.kyoto-u.ac.jp.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: rkaji@tokushima-u.ac.jp.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D010244:Bulbar Palsy, Progressive / Q000209:etiology*; D004252:DNA Mutational Analysis; D004576:Electromyography; D005192:Family Health; D005207:Fasciculation / Q000209:etiology*; D005260:Female; D006801:Humans; D007564:Japan; D016547:Kinesins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D009431:Neural Conduction / Q000235:genetics; D015419:Spastic Paraplegia, Hereditary / Q000150:complications* / Q000235:genetics
chemical_list: C500506:KIF5A protein, human; D016547:Kinesins
keywords: Amyotrophic lateral sclerosis; Dysarthria; Elderly asymptomatic carriers; Fasciculation; Hereditary spastic paraplegia; SPG10; Whole exome sequencing