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Neurofilament light mutation causes hereditary motor and sensory neuropathy with pyramidal signs
Author(s) -
Hashiguchi Akihiro,
Higuchi Yujiro,
Nomura Miwa,
Nakamura Tomonori,
Arata Hitoshi,
Yuan Junhui,
Yoshimura Akiko,
Okamoto Yuji,
Matsuura Eiji,
Takashima Hiroshi
Publication year - 2014
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/jns.12102
Subject(s) - missense mutation , hereditary motor and sensory neuropathy , amyotrophic lateral sclerosis , pathology , mutation , neurofilament , neuroscience , medicine , corpus callosum , biology , gene , genetics , disease , immunohistochemistry
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.