title: Genetic analysis of amyotrophic lateral sclerosis in the Slovenian population.
abstract: Amyotrophic lateral sclerosis (ALS) is a complex fatal neurodegenerative disease characterized by progressive degeneration and loss of upper motor neurons in the cerebral cortex and lower motor neurons in brainstem and spinal cord. We established the frequencies of mutations in 4 major ALS-associated genes, SOD1, TARDBP, FUS, and C9ORF72 in a representative cohort of 85 Slovenian patients with sporadic form of ALS. Pathogenic massive hexanucleotide repeat expansion mutation in C9ORF72 was detected in 5.9% of patients and was the most common cause of the disease. In the remaining 3 genes, we identified 4 changes in 3 patients, p.Val14Met in SOD1, silent mutation p.Arg522Arg in FUS, and p.Gly93Cys in SOD1 together with a novel synonymous variant c.990A>G (p.Leu330Leu) in TARDBP gene, respectively. This study represents the first genetic screening of major causative genes for ALS in a cohort of sporadic ALS patients from Slovenia and is according to our knowledge the first such study in Slavic population. Overall, we genetically characterized 8.2% sporadic ALS patients.
authors.affiliation: Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Vrabec
authors.affiliation: Institute of Clinical Neurophysiology, Division of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Blaž
authors.initials: B
authors.lastname: Koritnik
authors.affiliation: Institute of Clinical Neurophysiology, Division of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Lea
authors.initials: L
authors.lastname: Leonardis
authors.affiliation: Institute of Clinical Neurophysiology, Division of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Leja
authors.initials: L
authors.lastname: Dolenc-Grošelj
authors.affiliation: Institute of Clinical Neurophysiology, Division of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Zidar
authors.affiliation: Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.
authors.forename: Bradley
authors.initials: B
authors.lastname: Smith
authors.affiliation: Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vance
authors.affiliation: Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Shaw
authors.affiliation: Department of Biotechnology, Jožef Štefan Institute, Ljubljana, Slovenia; Biomedical Research Institute, Ljubljana, Slovenia.
authors.forename: Boris
authors.initials: B
authors.lastname: Rogelj
authors.affiliation: Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Damjan
authors.initials: D
authors.lastname: Glavač
authors.affiliation: Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. Electronic address: metka.ravnik@gmail.com.
authors.forename: Metka
authors.initials: M
authors.lastname: Ravnik-Glavač
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D000073885:C9orf72 Protein; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D017524:Slovenia / Q000453:epidemiology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins; C000599550:FUS protein, human; D011506:Proteins; D034702:RNA-Binding Protein FUS; C000606290:SOD1 protein, human; C000598624:TARDBP protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: ALS genetic analysis; C9ORF72; FUS; SOD1; Slovenian population; TARDBP