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.
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.


OBJECTIVE
To screen the SOD1 gene in search of potential mutations and to obtain clinical and pathological data for 2 Japanese families with ALS.


METHODS
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.
Takehisa
Y
Y
Department of Neuropsychiatry, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Ujike
H
H
Ishizu
H
H
Terada
S
S
Haraguchi
T
T
Tanaka
Y
Y
Nishinaka
T
T
Nobukuni
K
K
Ihara
Y
Y
Namba
R
R
Yasuda
T
T
Nishibori
M
M
Hayabara
T
T
Kuroda
S
S
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology; D005260:Female; D006801:Humans; D006818:Hyalin / Q000648:ultrastructure*; D002479:Inclusion Bodies / Q000648:ultrastructure*; D016631:Lewy Bodies / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*
D013482:Superoxide Dismutase