Genetic Epidemiology of Amyotrophic Lateral Sclerosis in Norway: A 2-Year Population-Based Study

• DOI: 10.1159/000525091
• Publication Date: 2022-05-16T21:00:32Z
• Authors: Cathrine Goberg O...; Øyvind Løvold Busk; Tori Navestad Aan...; Karl Bjørnar Alst...; Ingrid Kristine B...; Geir Julius Braathen; Kristin Lif Breivik; Natasha Demic; Heidi Øyen Flemmen; Erika Hallerstig; Ineke HogenEsch; Øystein Lunde Holla; Anne Berit Jøntvedt; Margitta T. Kampman; Grethe Kleveland; Helene Ballo Kvernmo; Unn Ljøstad; Angelina Maniaol; Åse Hagen Morsund; Ola Nakken; Camilla Novy; Tiina Rekand; Katrin Schlüter; Stephan Schüler; Kristian Tveten; Ole-Bjørn Tysnes; Trygve Holmøy; Helle Høyer
• Keywords: 0301 basic medicine; Molecular Epidemiology; 03 medical and health sciences; Superoxide Dismutase-1; 0302 clinical medicine; C9orf72 Protein; Amyotrophic Lateral Sclerosis; 610; Humans; Neurodegenerative Diseases; 3. Good health

<b><i>Background:</i></b> Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. In Europe, disease-causing genetic variants have been identified in 40–70% of familial ALS patients and approximately 5% of sporadic ALS patients. In Norway, the contribution of genetic variants to ALS has not yet been studied. In light of the potential development of personalized medicine, knowledge of the genetic causes of ALS in a population is becoming increasingly important. The present study provides clinical and genetic data on familial and sporadic ALS patients in a Norwegian population-based cohort. <b><i>Methods:</i></b> Blood samples and clinical information from ALS patients were obtained at all 17 neurological departments throughout Norway during a 2-year period. Genetic analysis of the samples involved expansion analysis of <i>C9orf72</i> and exome sequencing targeting 30 known ALS-linked genes. The variants were classified using genotype-phenotype correlations and bioinformatics tools. <b><i>Results:</i></b> A total of 279 ALS patients were included in the study. Of these, 11.5% had one or several family members affected by ALS, whereas 88.5% had no known family history of ALS. A genetic cause of ALS was identified in 31 individuals (11.1%), among which 18 (58.1%) were familial and 13 (41.9%) were sporadic. The most common genetic cause was the <i>C9orf72</i> expansion (6.8%), which was identified in 8 familial and 11 sporadic ALS patients. Pathogenic or likely pathogenic variants of <i>SOD1</i> and <i>TBK1</i> were identified in 10 familial and 2 sporadic cases. <i>C9orf72</i> expansions dominated in patients from the Northern and Central regions, whereas <i>SOD1</i> variants dominated in patients from the South-Eastern region. <b><i>Conclusion:</i></b> In the present study, we identified several pathogenic gene variants in both familial and sporadic ALS patients. Restricting genetic analysis to only familial cases would miss more than 40 percent of those with a disease-causing genetic variant, indicating the need for genetic analysis in sporadic cases as well.