Genetic analysis of the SOD1 and C9ORF72 genes in Hungarian patients with amyotrophic lateral sclerosis

Kornélia Tripolszki, Bernadett Csányi, Dóra Nagy, Antonia Ratti, Cinzia Tiloca, Vincenzo Silani, Éva Kereszty, Nóra Török, László Vécsei, József I. Engelhardt, Péter Klivényi, Nikoletta Nagy, Márta Széll

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)195.e1-195.e5
JournalNeurobiology of Aging
Volume53
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Chromosomes, Human, Pair 9
Amyotrophic Lateral Sclerosis
Open Reading Frames
Genes
Mutation
Nonsense Codon
Motor Neurons
Superoxide Dismutase-1
Neurodegenerative Diseases
Amino Acids

Keywords

  • ALS
  • C9ORF72
  • Mutation screening
  • Repeat expansion
  • SOD1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Genetic analysis of the SOD1 and C9ORF72 genes in Hungarian patients with amyotrophic lateral sclerosis. / Tripolszki, Kornélia; Csányi, Bernadett; Nagy, Dóra; Ratti, Antonia; Tiloca, Cinzia; Silani, Vincenzo; Kereszty, Éva; Török, Nóra; Vécsei, László; Engelhardt, József I.; Klivényi, Péter; Nagy, Nikoletta; Széll, Márta.

In: Neurobiology of Aging, Vol. 53, 01.05.2017, p. 195.e1-195.e5.

Research output: Contribution to journalArticle

Tripolszki, K, Csányi, B, Nagy, D, Ratti, A, Tiloca, C, Silani, V, Kereszty, É, Török, N, Vécsei, L, Engelhardt, JI, Klivényi, P, Nagy, N & Széll, M 2017, 'Genetic analysis of the SOD1 and C9ORF72 genes in Hungarian patients with amyotrophic lateral sclerosis', Neurobiology of Aging, vol. 53, pp. 195.e1-195.e5. https://doi.org/10.1016/j.neurobiolaging.2017.01.016
Tripolszki, Kornélia ; Csányi, Bernadett ; Nagy, Dóra ; Ratti, Antonia ; Tiloca, Cinzia ; Silani, Vincenzo ; Kereszty, Éva ; Török, Nóra ; Vécsei, László ; Engelhardt, József I. ; Klivényi, Péter ; Nagy, Nikoletta ; Széll, Márta. / Genetic analysis of the SOD1 and C9ORF72 genes in Hungarian patients with amyotrophic lateral sclerosis. In: Neurobiology of Aging. 2017 ; Vol. 53. pp. 195.e1-195.e5.
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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.",
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