Familial ALS with extreme phenotypic variability due to the I113T SOD1 mutation.
We describe a large family with amyotrophic lateral sclerosis (ALS) caused by an I113T mutation in superoxide dismuatse type 1 (SOD1). The proband developed symptoms typical for ALS at age 39 years and is still walking five years later. Marked phenotypic variability is manifested by her mother with onset of gait difficulty and decision-making problems at age 67 years and a five-year course marked by progressive mild upper motor neuron weakness, frontotemporal dementia and chorea. An aunt's initial symptoms included foot numbness and an uncle with the mutation is asymptomatic. Penetrance is only 50% at age 60 years and 88% at age 80 years with an 86-year-old woman harboring the mutation and having a normal neurologic examination. This family highlights the extreme variability in age of onset, clinical manifestations, disease progression and penetrance due to the I113T SOD1 mutation.
Lopate
Glenn
G
Washington University School of Medicine, Department of Neurology, Saint Louis, Missouri 63110, USA. lopateg@neuro.wustl.edu <lopateg@neuro.wustl.edu>
Baloh
Robert H
RH
Al-Lozi
Muhammad T
MT
Miller
Timothy M
TM
Fernandes Filho
J Americo
JA
Ni
Oliver
O
Leston
Alison
A
Florence
Julaine
J
Schierbecker
Jeanine
J
Allred
Peggy
P
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D018450:Disease Progression; D005192:Family Health; D005260:Female; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D055815:Young Adult
C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1