Heterozygous SOD1 D90A mutation presenting as slowly progressive predominant upper motor neuron amyotrophic lateral sclerosis.
Of all the SOD1 gene mutations described, uniquely the D90A mutation has been identified in recessive, dominant, and apparently sporadic cases. We describe a patient with a sporadic form of amyotrophic lateral sclerosis (ALS) in which a heterozygous A > C exchange at position 272 in the SOD1 gene was detected. This mutation results in an amino acid substitution of alanine for aspartate at position 90 (D90A). The patient had a 12-year history of disease characterized by slow progression. Clinical examination at last follow-up revealed predominant upper motor neuron (p-UMN) involvement, with atrophies only in distal muscle of upper limbs. Electrophysiological examination revealed lower and upper motor neuron involvement. Family history was negative for neurological disease. This report shows that D90A in heterozygous state may cause p-UMN phenotype with very slow progression.
Luigetti
Marco
M
Istituto di Neurologia Pol A: Gemelli, Largo Gemelli 8, 00168 Rome, Italy. mluigetti@gmail.com
Conte
Amelia
A
Madia
Francesca
F
Marangi
Giuseppe
G
Zollino
Marcella
M
Mancuso
Irene
I
Dileone
Michele
M
Del Grande
Alessandra
A
Di Lazzaro
Vincenzo
V
Tonali
Pietro Attilio
PA
Sabatelli
Mario
M
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005190:Family; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000235:genetics* / Q000503:physiopathology*; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013997:Time Factors
C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
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