Ontology highlight
ABSTRACT: Background
Up to 7% of patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) remain genetically undiagnosed after routine genetic testing. These patients are thought to carry deep intronic variants, structural variants or splicing alterations not detected through multiplex ligation-dependent probe amplification or exome sequencing.Methods
RNA was extracted from seven muscle biopsy samples of patients with genetically undiagnosed DMD/BMD after routine genetic diagnosis. RT-PCR of the DMD gene was performed to detect the presence of alternative transcripts. Droplet digital PCR and whole-genome sequencing were also performed in some patients.Results
We identified an alteration in the mRNA level in all the patients. We detected three pseudoexons in DMD caused by deep intronic variants, two of them not previously reported. We also identified a chromosomal rearrangement between Xp21.2 and 8p22. Furthermore, we detected three exon skipping events with unclear pathogenicity.Conclusion
These findings indicate that mRNA analysis of the DMD gene is a valuable tool to reach a precise genetic diagnosis in patients with a clinical and anatomopathological suspicion of dystrophinopathy that remain genetically undiagnosed after routine genetic testing.
SUBMITTER: Segarra-Casas A
PROVIDER: S-EPMC10313949 | biostudies-literature | 2023 Jun
REPOSITORIES: biostudies-literature
Segarra-Casas Alba A Domínguez-González Cristina C Hernández-Laín Aurelio A Sanchez-Calvin Maria Teresa MT Camacho Ana A Rivas Eloy E Campo-Barasoain Andrea A Madruga Marcos M Ortez Carlos C Natera-de Benito Daniel D Nascimento Andrés A Codina Anna A Rodriguez Maria Jose MJ Gallano Pia P Gonzalez-Quereda Lidia L
Journal of medical genetics 20221219 6
<h4>Background</h4>Up to 7% of patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) remain genetically undiagnosed after routine genetic testing. These patients are thought to carry deep intronic variants, structural variants or splicing alterations not detected through multiplex ligation-dependent probe amplification or exome sequencing.<h4>Methods</h4>RNA was extracted from seven muscle biopsy samples of patients with genetically undiagnosed DMD/BMD after routine ...[more]