title: Familial ALS with extreme phenotypic variability due to the I113T SOD1 mutation.
abstract: 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.
authors.affiliation: Washington University School of Medicine, Department of Neurology, Saint Louis, Missouri 63110, USA. lopateg@neuro.wustl.edu <lopateg@neuro.wustl.edu>
authors.forename: Glenn
authors.initials: G
authors.lastname: Lopate
authors.forename: Robert H
authors.initials: RH
authors.lastname: Baloh
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Al-Lozi
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Miller
authors.forename: J Americo
authors.initials: JA
authors.lastname: Fernandes Filho
authors.forename: Oliver
authors.initials: O
authors.lastname: Ni
authors.forename: Alison
authors.initials: A
authors.lastname: Leston
authors.forename: Julaine
authors.initials: J
authors.lastname: Florence
authors.forename: Jeanine
authors.initials: J
authors.lastname: Schierbecker
authors.forename: Peggy
authors.initials: P
authors.lastname: Allred
mesh_terms: 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
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1