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Variance of age at onset in a Japanese family with amyotrophic lateral sclerosis associated with a novel cu/zn superoxide dismutase mutation
Author(s) -
Aoki Masashi,
Abe Koji,
Houi Kouji,
Ogasawara Masahito,
Matsubara Yoichi,
Kobayashi Takaaki,
Mochio Soichiro,
Narisawa Kuniaki,
Itoyama Yasuto
Publication year - 1995
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410370518
Subject(s) - amyotrophic lateral sclerosis , superoxide dismutase , exon , valine , mutation , sod1 , point mutation , medicine , age of onset , genetics , endocrinology , amino acid , gene , disease , biology , oxidative stress
Although about 5 to 10% of amyotrophic lateral sclerosis (ALS) cases are familial, the pathophysiology of ALS remians unknown. A new point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD) gene, resulting in an amino acid substitution of leucine 84 by valine (L84V), in a Japanese patient with familial ALS (FALS) was identified. This L84V substitution was not observed in 57 normal Japanese control subjects. The enzymatic activities of Cu/Zn SOD of skin fibroblasts were significantly reduced to 75% of the control level in the affected patient. The progression of the disease with this mutation is very rapid, but the age at onset varies with sex or generation within a family.