Common mutations of interest for the diagnosis of amyotrophic lateral sclerosis: how common are common mutations in ALS genes?


Perrone B and Conforti FL. Expert Rev Mol Diagn 2020.


Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease predominantly affecting upper and lower motor neurons. Diagnosis of this devastating pathology is very difficult because the high degree of clinical heterogeneity with which it occurs and until now, no truly effective treatment exists. Areas covered: Molecular diagnosis may be a valuable tool for dissecting out ALS complex heterogeneity and for identifying new molecular mechanisms underlying the characteristic selective

degeneration and death of motor neurons. To date, pathogenic variants in ALS genes are known to be present in up to 70% of familial and 10% of apparently sporadic ALS cases, and can be associated with risks for ALS only, or risks for other neurodegenerative diseases. This paper shows the procedure currently used in diagnostic laboratories to investigate most frequent mutations in ALS and evaluating the utility of involved molecular techniques as potential tools to discriminate "common mutations" in ALS patients. Expert opinion: Genetic testing may allow for establishing an accurate pathological diagnosis and a more precise stratification of patient groups in future drug trials.