title: Genetic analysis of the SOD1 and C9ORF72 genes in Hungarian patients with amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons. To date, more than 20 genes have been implicated in ALS, and of these, the 2 most frequently mutated are the superoxide dismutase 1 (SOD1) gene and the chromosome 9 open reading frame 72 (C9ORF72) gene. In this study, we aimed to investigate the contribution of these 2 Mendelian genes to the development of the disease in Hungarian ALS patients (n = 66). Direct sequencing of the SOD1 gene revealed a novel (p.Lys91ArgfsTer8) and 3 recurrent heterozygous mutations (p.Val14Met, p.Asp90Ala, and p.Leu144Phe) in 5 patients. The novel p.Lys91ArgfsTer8 mutation led to a frameshift causing the addition of 8 new amino acids, including a premature stop codon at position 99. The GGGGCC hexanucleotide repeat expansion of the C9ORF72 gene was present in 1 ALS patient. This study represents the first genetic analysis of 2 major ALS causative genes in a cohort of Hungarian ALS patients and contributes to the further understanding of the genetic and phenotypic diversity of ALS.
authors.affiliation: Department of Medical Genetics, University of Szeged, Szeged, Hungary.
authors.forename: Kornélia
authors.initials: K
authors.lastname: Tripolszki
authors.affiliation: Department of Forensic Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Csányi
authors.affiliation: Department of Medical Genetics, University of Szeged, Szeged, Hungary.
authors.forename: Dóra
authors.initials: D
authors.lastname: Nagy
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Ratti
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Tiloca
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
authors.affiliation: Department of Forensic Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Kereszty
authors.affiliation: Department of Neurology, University of Szeged, Szeged, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Török
authors.affiliation: Department of Neurology, University of Szeged, Szeged, Hungary; MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.affiliation: Department of Neurology, University of Szeged, Szeged, Hungary.
authors.forename: József I
authors.initials: JI
authors.lastname: Engelhardt
authors.affiliation: Department of Neurology, University of Szeged, Szeged, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Klivényi
authors.affiliation: Department of Medical Genetics, University of Szeged, Szeged, Hungary; MTA SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary. Electronic address: nikoletta.nagy@gmail.com.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Nagy
authors.affiliation: Department of Medical Genetics, University of Szeged, Szeged, Hungary; MTA SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary.
authors.forename: Márta
authors.initials: M
authors.lastname: Széll
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000073885:C9orf72 Protein / Q000235:genetics*; D015331:Cohort Studies; D042622:DNA Repeat Expansion; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006814:Hungary; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000072105:Superoxide Dismutase-1 / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C000606290:SOD1 protein, human; D000072105:Superoxide Dismutase-1
keywords: ALS; C9ORF72; Mutation screening; Repeat expansion; SOD1