ABSTRACT
We report a patient with sporadic amyotrophic lateral sclerosis (ALS) with a novel fusion in malignant liposarcoma (FUS) gene mutation whose neurological signs were conspicuous left-sided rigidity and apraxia. A novel heterozygous guanine (G)-to-thymine (T) transition at position 1392, c.1392G>T, leading to a methionine-to-isoleucine substitution (p.Met464Ile), was found in exon13 of FUS. Re-sequencing of the genes for superoxide dismutase 1 (SOD1) and transactive response-DNA binding protein (TARDBP) revealed no mutations. The present findings suggest that this novel FUS mutation (p.Met464Ile) is related to manifestations of ALS as well as clinical features of corticobasal degeneration.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/pathology , Brain/pathology , RNA-Binding Protein FUS/genetics , Base Sequence , Humans , Molecular Sequence Data , MutationABSTRACT
We investigated the optimum doses of phenytoin for treatment of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Oral and intraperitoneal administrations of 0.25 to 1.0mg per mouse (12.5-50mg/kg) 3 times a week improved the clinical course. Intraperitoneal injections of 1.0mg phenytoin were the most effective, as a significant reduction in EAE severity was seen after only 2 administrations with that protocol. Treatment efficacy was associated with amelioration of cellular infiltrates in the CNS, and an increase in CD4(+)Foxp3(+) and CD4(+)CD25(+)CD127(-) regulatory T cells as well as CD8(+) suppressor/cytotoxic T cells in blood.
