Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease involving both the brain and spinal cord. While it has traditionally been perceived to be a syndrome primarily affecting motor neurons, there is increasing recognition that additional areas within the frontal and temporal lobes are involved to varying degrees in a subset of individuals. In addition, other systems outside the nervous system may be involved, such as bone (Paget disease of the bone) and muscle (inclusion body myopathy). The location and extent of the degeneration determines the clinical picture, which by definition includes motor decline, and may include cognitive and/or behavioral symptoms as well. There is wide variability in presentation, progression, and survival (PMID 28980624).
About half of familial ALS cases have a pathogenic variant in one of 30 genes associated with the disease. Of these, the four most commonly-implicated genes are C9orf72, SOD1, FUS and TARDBP (TDP-43) (PMID 20301623).
Pathogenic variants in SOD1 are implicated in 15-20% of familial ALS, and in 3% of sporadic ALS. Patients with a pathogenic SOD1 variant are expected to respond to SOD1-targeted therapy (Tofersen), which has recently been approved by the FDA.
Analysis of the C9orf72 gene for repeat expansions is also available from this laboratory. Sequencing of the FUS and TARDBP genes is also available on specific request. However, onward referral for a larger gene panel may be more clinically-appropriate and cost-effective. Please contact our laboratory to discuss additional testing, if required.
Genetics - Molecular Pathology
MOLP
ALS
Amyotrophic Lateral Sclerosis
4 weeks
4583