title: Marked intrafamilial phenotypic variation in a family with SOD1 C111Y mutation.
abstract: Our objectives were to identify the disease-causing mutation in, and report on the clinical features of, a Japanese family that had coexisting phenotypes of amyotrophic lateral sclerosis and spinal muscular atrophy. The family comprised nine patients (six men and three women). We reviewed their clinical records and performed mutation analysis of the copper/zinc superoxide dismutase (SOD1) gene in some of these patients. The patients either had a rapid (n=7) or an extremely long (n=2) clinical course. The mean age at onset was 39.0±13.7 years (range 20-68 years). The initial symptoms were bulbar palsy (n=2), upper (n=4) or lower (n=2) limb muscle weakness, or leg cramps (n=1). The total disease duration varied widely, ranging from one year to >69 years. We identified a SOD1 C111Y mutation among patients in this family. In conclusion, the family showed a marked intrafamilial phenotypic variation associated with the SOD1 C111Y mutation. Elucidating the biological basis of disease expression in patients with the SOD1 C111Y mutation may provide us with useful information to develop therapeutic approaches and to prevent disease progression.
authors.affiliation: Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan. anakamu@shinshu-u.ac.jp
authors.forename: Akinori
authors.initials: A
authors.lastname: Nakamura
authors.forename: Akiyo
authors.initials: A
authors.lastname: Hineno
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yoshida
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sekijima
authors.forename: Naoko
authors.initials: N
authors.lastname: Hanaoka-Tachibana
authors.forename: Yo-Ichi
authors.initials: Y
authors.lastname: Takei
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohara
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011859:Radiography; 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