Genetic diagnosis of Duchenne and Becker muscular dystrophy through mRNA analysis: new splicing events
A Segarra-Casas, C Domínguez-González… - … of medical genetics, 2023 - jmg.bmj.com
A Segarra-Casas, C Domínguez-González, A Hernández-Laín, MT Sanchez-Calvin…
Journal of medical genetics, 2023•jmg.bmj.comBackground 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 …
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 …
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.
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