title: [Familial amyotrophic lateral sclerosis showing variable clinical courses with (Leu84-->Val) mutation of Cu/Zn superoxide dismutase].
abstract: A family with autosomal-dominant amyotrophic lateral sclerosis with histopathological confirmation on autopsy was described. A 42-year-old female proband showed the signs and symptoms only in the lower limbs characteristic of lower motor neuron involvement at the onset. ALS had been diagnosed in other five members in three generations of her family. The mean +/- SD age of onset of the disease was 42.5 +/- 9.3 years with a range of 30 to 51 years. The mean +/- SD duration of the disease (n = 5, excluding the proband) was 56 +/- 70 months with a range of 7 to 180 months. Molecular genetic studies showed a T-to-G transversion that results in the substitution of valine for leucine84 in exon 4 of the Cu/Zn superoxide dismutase (SOD) gene on chromosome 21 in a proband. This mutation is identical to that found in the Japanese family with autosomal-dominant ALS characterized by short duration of the disease, within 1.5 years, in all the affected family members. Therefore, the clinical phenotype, especially the duration of the disease seems to be highly variable even in the families with the identical mutation of the Cu/Zn SOD gene.
authors: Department of Medical Genetics, Nara Medical University, Japan.
authors: A
authors: A
authors: Ohnishi
authors: S
authors: S
authors: Miyazaki
authors: Y
authors: Y
authors: Murai
authors: S
authors: S
authors: Ueno
authors: H
authors: H
authors: Sakai
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D005192:Family Health; D005260:Female; D006801:Humans; D007930:Leucine; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D013482:Superoxide Dismutase / Q000235:genetics*; D014633:Valine
chemical_list: D013482:Superoxide Dismutase; D007930:Leucine; D014633:Valine