RT Journal Article
SR Electronic
T1 Systematic evaluation of genetic mutations in ALS: a population-based study
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 1190
OP 1193
DO 10.1136/jnnp-2022-328931
VO 93
IS 11
A1 Maurizio Grassano
A1 Andrea Calvo
A1 Cristina Moglia
A1 Luca Sbaiz
A1 Maura Brunetti
A1 Marco Barberis
A1 Federico Casale
A1 Umberto Manera
A1 Rosario Vasta
A1 Antonio Canosa
A1 Sandra D’Alfonso
A1 Lucia Corrado
A1 Letizia Mazzini
A1 Clifton Dalgard
A1 Ramita Karra
A1 Ruth Chia
A1 Bryan Traynor
A1 Adriano Chiò
YR 2022
UL http://jnnp.bmj.com/content/93/11/1190.abstract
AB 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.