Multiple system degeneration with basophilic inclusions in Japanese ALS patients with FUS mutation

Autor: Nobuyuki Nukina, Yuko Nagara, H. Tashiro, Yasumasa Ohyagi, Shiro Miura, Hirokazu Furuya, Akiko Iwaki, Toshihiro Hokonohara, Jun Ichi Kira, Takahisa Tateishi, Yasuyuki Fukumaki, Ryo Yamasaki, Hitoshi Kikuchi, Toru Iwaki
Rok vydání: 2009
Předmět:
Adult
Male
Pathology
medicine.medical_specialty
Genotype
Biopsy
Biology
DNA
Antisense
Pathology and Forensic Medicine
Young Adult
Cellular and Molecular Neuroscience
Central tegmental tract
medicine
Inferior olivary nucleus
Humans
Missense mutation
Age of Onset
Amyotrophic lateral sclerosis
Endoplasmic Reticulum Chaperone BiP
Inclusion Bodies
Neurologic Examination
Neurons
Tomography
Emission-Computed
Single-Photon
Muscle Weakness
Spinocerebellar tract
Electromyography
Amyotrophic Lateral Sclerosis
Brain
Autosomal dominant trait
Anatomy
Middle Aged
medicine.disease
Magnetic Resonance Imaging
Phenotype
Superior cerebellar peduncle
medicine.anatomical_structure
nervous system
Glial cytoplasmic inclusion
Mutation
Nerve Degeneration
Disease Progression
RNA-Binding Protein FUS
Female
Neurology (clinical)
Zdroj: Acta Neuropathologica. 119:355-364
ISSN: 1432-0533
0001-6322
DOI: 10.1007/s00401-009-0621-1
Popis: Mutations in the fused in sarcoma gene (FUS) were recently found in patients with familial amyotrophic lateral sclerosis (ALS). The present study aimed to clarify unique features of familial ALS caused by FUS mutation in the Japanese population. We carried out clinical, neuropathological, and genetic studies on a large Japanese pedigree with familial ALS. In six successive generations of this family, 16 individuals of both sexes were affected by progressive muscle atrophy and weakness, indicating an autosomal dominant trait. Neurological examination of six patients revealed an age at onset of 48.2 ± 8.1 years in fourth generation patients, while it was 31 and 20 years in fifth and sixth generation patients, respectively. Motor paralysis progressed rapidly in these patients, culminating in respiratory failure within 1 year. The missense mutation c.1561 C>T (p.R521C) was found in exon 15 of FUS in the four patients examined. Neuropathological study of one autopsied case with the FUS mutation revealed multiple system degeneration in addition to upper and lower motor neuron involvement: the globus pallidus, thalamus, substantia nigra, cerebellum, inferior olivary nucleus, solitary nucleus, intermediolateral horn, Clarke’s column, Onuf’s nucleus, central tegmental tract, medial lemniscus, medial longitudinal fasciculus, superior cerebellar peduncle, posterior column, and spinocerebellar tract were all degenerated. Argyrophilic and basophilic neuronal or glial cytoplasmic inclusions immunoreactive for FUS, GRP78/BiP, p62, and ubiquitin were detected in affected lesions. The FUS R521C mutation in this Japanese family caused familial ALS with pathological features of multiple system degeneration and neuronal basophilic inclusions.
Databáze: OpenAIRE
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