Amyotrophic lateral sclerosis and primary lateral sclerosis comprehensive panel [38 genes]
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a prevalence of 5.4/100,000 (Chiò et al., 2013). Even though most cases are of sporadic presentation, previous family history exists in 10% of patients. Pathogenic variants in the C9orf72, SOD1, TARDBP, and FUS genes explain almost two thirds of the familial forms (25%, 20%, 5%, and 5% respectively). In the C9orf72 gene, a single genetic alteration associated with amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia has been detected, consisting of a (GGGGCC)n repeat expansion not detectable by next generation sequencing.
Primary lateral sclerosis (PLS) is characterized by isolated involvement of upper motor neurons, which distinguishes it from amyotrophic lateral sclerosis, where lower motor neurons are also compromised. The diagnosis of PLS is made by excluding disease causes such as spastic paraplegia, multiple sclerosis, metabolic disease, or myelopathy
Priority Genes : Genes where there is sufficient evidence (clinical and functional) to consider them associated with the disease; they are included in the clinical practice guidelines.
Secondary Genes: Genes related to the disease, but with a lower level of evidence or that constitute sporadic cases.
* Candidate Genes: Not enough evidence in humans, but potentially associated with the disease.
- ALS2, FIG4, SPG11, TBK1: Primary lateral sclerosis
- CHCHD10, SQSTM1, TBK1: Primary lateral sclerosis with/without frontotemporal dementia
- SLC52A2, SLC52A3: Brown-Vialetto-Van Laere/Fazio-Londe syndrome
ALS1, ALS2, ALS4, ALS5, ALS6, ALS8, ALS9, ALS10, ALS11, ALS12, ALS14, ALS15, ALS16, ALS17, ALS18, ALS19, ALS20, ALS21, FTDALS2, FTDALS3, FTDALS4.
- Chiò A, Logroscino G, Traynor BJ, Collins J, Simeone JC, Goldstein LA, White LA. Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology. 2013;41(2):118-30.