title: Identification of two novel mutations in the Cu/Zn superoxide dismutase gene with familial amyotrophic lateral sclerosis: mass spectrometric and genomic analyses.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. The majority of patients are sporadic cases, while 5-10% of the patients have a family history of ALS (fALS). Mutations in the gene that encodes cytoplasmic Cu/Zn superoxide dismutase (SOD1) have been identified in about 25% of fALS cases. Although the precise pathogenesis of ALS is still unknown, experimental studies including animal models suggest that fALS is caused by the toxic gain-of-function of the SOD1 mutant. We have analyzed not only SOD1 gene mutation by genomic sequencing, but also SOD1 mutant protein by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). We analyzed 33 fALS patients and found 10 mutations in SOD1 gene, in which two were novel: Asp101His substitution in exon 4 and Gly141Glu substitution in exon 5. Here, we present their mass spectrometric protein analyses and clinical features.
authors.affiliation: Department of Neurology D4, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Sato
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Kei
authors.initials: K
authors.lastname: Fukada
authors.forename: Fuminobu
authors.initials: F
authors.lastname: Sugai
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhou
authors.forename: Tatsusada
authors.initials: T
authors.lastname: Okuno
authors.forename: Seiichi
authors.initials: S
authors.lastname: Nagano
authors.forename: Shuji
authors.initials: S
authors.lastname: Hirata
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Saburo
authors.initials: S
authors.lastname: Sakoda
mesh_terms: D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology / Q000235:genetics*; D001224:Aspartic Acid / Q000235:genetics; D002853:Chromatography, Liquid / Q000379:methods; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons; D005192:Family Health; D005260:Female; D018698:Glutamic Acid / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006639:Histidine / Q000235:genetics; D006801:Humans; D008297:Male; D008967:Molecular Biology / Q000379:methods; D008969:Molecular Sequence Data; D009154:Mutation; D011233:Precipitin Tests / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; D006639:Histidine; D013482:Superoxide Dismutase; D005998:Glycine