A novel deep intronic variant in the DMD gene causes Duchenne muscular dystrophy by pseudoexon activation encoding a nonsense codon.
Gene
; 930: 148862, 2024 Dec 20.
Article
en En
| MEDLINE
| ID: mdl-39151676
ABSTRACT
Dystrophinopathies are a group of neuromuscular disorders, inherited in an X-linked recessive manner, caused by pathogenic variants in the DMD gene. Copy number variation detection and next generation sequencing allow the detection of around 99 % of the pathogenic variants. However, some patients require mRNA studies from muscle biopsies to identify deep intronic pathogenic variants. Here, we report a child suspected of having Duchenne muscular dystrophy, with a muscle biopsy showing dystrophin deficiency, and negative molecular testing for deletions, duplications, and small variants. mRNA analysis from muscle biopsy revealed a pseudoexon activation that introduce a premature stop codon into the reading frame. gDNA sequencing allowed to identified a novel variant, c.832-186 T>G, which creates a cryptic donor splice site, recognizing the underlying mechanism causing the pseudoexon insertion. This case highlights the usefulness of the mRNA analysis from muscle biopsy when routine genetic testing is negative and clinical suspicion of dystrophinopathies remains the main clinical diagnosis suspicion.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Intrones
/
Distrofina
/
Codón sin Sentido
/
Distrofia Muscular de Duchenne
Límite:
Child
/
Humans
/
Male
Idioma:
En
Revista:
Gene
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos