Concurrent sodium channelopathies and amyotrophic lateral sclerosis supports shared pathogenesis.
Amyotroph Lateral Scler Frontotemporal Degener
; 21(7-8): 627-630, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32619119
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is an invariably fatal adult-onset neurodegenerative disorder; approximately 10% of ALS is monogenic but all ALS exhibits significant heritability. The skeletal muscle sodium channelopathies are a group of inherited, non-dystrophic ion channel disorders caused by heterozygous point mutations in the SCN4A gene, leading to clinical manifestations of congenital myotonia, paramyotonia, and periodic paralysis syndromes. We provide clinical and genetic evidence of concurrence of these two rare disorders which implies a possible shared underlying pathophysiology in two patients. We then identify an enrichment of ALS-associated mutations in another sodium channel, SCN7A, from whole genome sequencing data of 4495 ALS patients and 1925 controls passing multiple testing correction (67 variants, p = 0.0002, Firth logistic regression). These findings suggest dysfunctional sodium channels may play a role upstream in the pathogenesis of ALS in a subset of patients, potentially opening the door to novel personalized medicine approaches.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canalopatias
/
Esclerose Lateral Amiotrófica
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Adult
/
Humans
Idioma:
En
Revista:
Amyotroph Lateral Scler Frontotemporal Degener
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido