title: Neurofilament light mutation causes hereditary motor and sensory neuropathy with pyramidal signs.
abstract: To identify novel mutations causing hereditary motor and sensory neuropathy (HMSN) with pyramidal signs, a variant of Charcot-Marie-Tooth disease (CMT), we screened 28 CMT and related genes in four members of an affected Japanese family. Clinical features included weakness of distal lower limb muscles, foot deformity, and mild sensory loss, then late onset of progressive spasticity. Electrophysiological studies revealed widespread neuropathy. Electron microscopic analysis showed abnormal mitochondria and mitochondrial accumulation in the neurons and Schwann cells. Brain magnetic resonance imaging (MRI) revealed an abnormally thin corpus callosum. In all four, microarrays detected a novel heterozygous missense mutation c.1166A>G (p.Y389C) in the gene encoding the light-chain neurofilament protein (NEFL), indicating that NEFL mutations can result in a HMSN with pyramidal signs phenotype.
authors.affiliation: Department of Neurology and Geriatrics, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima City, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hashiguchi
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Miwa
authors.initials: M
authors.lastname: Nomura
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Arata
authors.forename: Junhui
authors.initials: J
authors.lastname: Yuan
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D004594:Electrophysiology; D005260:Female; D020022:Genetic Predisposition to Disease; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000235:genetics*; D009474:Neurons / Q000648:ultrastructure*; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D012583:Schwann Cells / Q000648:ultrastructure*
chemical_list: D016900:Neurofilament Proteins; C044882:neurofilament protein L
keywords: Charcot-Marie-Tooth disease; gene chip array; hereditary motor and sensory neuropathy with pyramidal signs; light-chain neurofilament protein (NEFL); mitochondrial accumulation