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Familial Amyotrophic Lateral Sclerosis With a Novel Leu126Ser Mutation in the Copper/Zinc Superoxide Dismutase Gene Showing Mild Clinical Features and Lewy Body–Like Hyaline Inclusions
Yasushi Takehisa, MD;
Hiroshi Ujike, MD, PhD;
Hideki Ishizu, MD, PhD;
Seishi Terada, MD;
Takashi Haraguchi, MD;
Yuji Tanaka, MD, PhD;
Tetsuya Nishinaka, MD, PhD;
Keigo Nobukuni, MD;
Yuetsu Ihara, MD, PhD;
Reiko Namba, MD;
Takeshi Yasuda, MD, PhD;
Masahiro Nishibori, MD, PhD;
Toshiyuki Hayabara, MD, PhD;
Shigetoshi Kuroda, MD, PhD
Arch Neurol. 2001;58:736-740.
Background Mutations in the SOD1 gene are responsible
for approximately 25% of all familial amyotrophic lateral sclerosis (ALS)
cases. However, the correlation between the clinical and pathological features
and the various SOD1 gene mutations has not been
well characterized.
Objectives To screen the SOD1 gene in search of potential
mutations and to obtain clinical and pathological data for 2 Japanese families
with ALS.
Design Clinical histories and neurological findings, gross and microscopic
pathological features, and DNA analysis of the SOD1
gene.
Results The 2 families with ALS showed a novel missense mutation in the SOD1 gene, which was heterozygous for point mutation TTG
to TCG, causing substitution of leucine for serine at codon 126 (Leu126Ser)
in exon 5. Clinically, patients showed slower disease progression and lack
of upper motor neuron signs. Neuropathologically, the autopsied patient showed
the form of familial ALS with posterior column involvement, and the pontocerebellar
tract and the dentate nuclei of the cerebellum were also involved. Furthermore,
abundant Lewy body–like hyaline inclusions were observed in the affected
motor and nonmotor neurons.
Conclusions Familial ALS with a novel Leu126Ser mutation in the SOD1 gene showed mild clinical features and lack of upper motor neuron
signs. We believe that Leu126Ser might be associated with the clinical features
and that the mutation site in the SOD1 gene and disease
duration might be associated with the formation of Lewy body–like hyaline
inclusions.
From the Departments of Neuropsychiatry (Drs Takehisa, Ujike, Ishizu,
Terada, Haraguchi, Tanaka, Nishinaka, and Kuroda) and Pharmacology (Dr Nishibori),
Okayama University Medical School; Department of Neurology, Clinical Research
Institute National Sanatorium Minamiokayama Hospital (Drs Nobukuni, Ihara,
Namba, and Hayabara); and the Department of Neurology, Kawasaki Medical School
Hospital (Dr Yasuda), Okayama, Japan.
Corresponding author and reprints: Yasushi Takehisa, Department of
Neuropsychiatry, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama
700-8558, Japan.
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