TY - JOUR T1 - Systematic evaluation of genetic mutations in ALS: a population-based study JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 1190 LP - 1193 DO - 10.1136/jnnp-2022-328931 VL - 93 IS - 11 AU - Maurizio Grassano AU - Andrea Calvo AU - Cristina Moglia AU - Luca Sbaiz AU - Maura Brunetti AU - Marco Barberis AU - Federico Casale AU - Umberto Manera AU - Rosario Vasta AU - Antonio Canosa AU - Sandra D’Alfonso AU - Lucia Corrado AU - Letizia Mazzini AU - Clifton Dalgard AU - Ramita Karra AU - Ruth Chia AU - Bryan Traynor AU - Adriano Chiò Y1 - 2022/11/01 UR - http://jnnp.bmj.com/content/93/11/1190.abstract N2 - Background A genetic diagnosis in Amyotrophic Lateral Sclerosis (ALS) can inform genetic counselling, prognosis and, in the light of incoming gene-targeted therapy, management. However, conventional genetic testing strategies are often costly and time-consuming.Objective To evaluate the diagnostic yield and advantages of whole-genome sequencing (WGS) as a standard diagnostic genetic test for ALS.Methods In this population-based cohort study, 1043 ALS patients from the Piemonte and Valle d’Aosta Register for ALS and 755 healthy individuals were screened by WGS for variants in 42 ALS-related genes and for repeated-expansions in C9orf72 and ATXN2.Results A total of 279 ALS cases (26.9%) received a genetic diagnosis, namely 75.2% of patients with a family history of ALS and 21.5% of sporadic cases. The mutation rate among early-onset ALS patients was 43.9%, compared with 19.7% of late-onset patients. An additional 14.6% of the cohort carried a genetic factor that worsen prognosis.Conclusions Our results suggest that, because of its high diagnostic yield and increasingly competitive costs, along with the possibility of retrospectively reassessing newly described genes, WGS should be considered as standard genetic testing for all ALS patients. Additionally, our results provide a detailed picture of the genetic basis of ALS in the general population. ER -