Genetic diagnosis of Duchenne and Becker muscular dystrophy through mRNA analysis : New splicing events
Segarra Casas, Alba (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Domínguez-González, C (Instituto de Salud Carlos III)
Hernández-Laín, Aurelia (Hospital 12 de Octubre (Madrid))
Sanchez-Calvin, Maria Teresa (Hospital 12 de Octubre (Madrid))
Camacho, Ana (Universidad Complutense de Madrid)
Rivas, Eloy (Pathology Universidad de Sevilla)
Campo-Barasoain, Andrea (Hospital Universitario Virgen Macarena)
Madruga, Marcos (Hospital Viamed Santa Ángela de la Cruz)
Ortez, Carlos (Institut de Recerca Sant Joan de Déu)
Natera-De Benito, Daniel (Institut de Recerca Sant Joan de Déu)
Nascimento, Andrés (Institut de Recerca Sant Joan de Déu)
Codina, Anna (Institut de Recerca Sant Joan de Déu)
Rodriguez, Maria Jose (Institut d'Investigació Biomèdica Sant Pau)
Gallano, Pia (Institut d'Investigació Biomèdica Sant Pau)
Gonzalez-Quereda, Lidia (Institut d'Investigació Biomèdica Sant Pau)

Date:	2023
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.
Grants:	Instituto de Salud Carlos III FIS PI18/01585 Ministerio de Ciencia, Innovación y Universidades FPU20/06692
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Journal of medical genetics, Vol. 60, Issue 6 (June 2023) , p. 615-619, ISSN 1468-6244

DOI: 10.1136/jmg-2022-108828
PMID: 36535754

5 p, 1.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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