Combinatorial effects of ion channel mis-splicing as a cause of myopathy in myotonic dystrophy.
J Clin Invest
; 134(1)2024 Jan 02.
Article
em En
| MEDLINE
| ID: mdl-38165037
ABSTRACT
Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder caused by an unstable expanded CTG repeat located in the 3'-UTR of the DM1 protein kinase (DMPK) gene. The pathogenic mechanism results in misregulated alternative splicing of hundreds of genes, creating the dilemma of establishing which genes contribute to the mechanism of DM1 skeletal muscle pathology. In this issue of the JCI, Cisco and colleagues systematically tested the combinatorial effects of DM1-relevant mis-splicing patterns in vivo and identified the synergistic effects of mis-spliced calcium and chloride channels as a major contributor to DM1 skeletal muscle impairment. The authors further demonstrated the therapeutic potential for calcium channel modulation to block the synergistic effects and rescue myopathy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Distrofia Miotônica
Limite:
Humans
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2024
Tipo de documento:
Article