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Lookup NU author(s): Alba Segarra Casas, Yolande Parkhurst, Robert Muni Lofra, Professor Chiara Marini Bettolo, Professor Volker StraubORCiD, Dr Ana TopfORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 by the authors. Duchenne and Becker muscular dystrophies, caused by pathogenic variants in DMD, are the most common inherited neuromuscular conditions in childhood. These diseases follow an X-linked recessive inheritance pattern, and mainly males are affected. The most prevalent pathogenic variants in the DMD gene are copy number variants (CNVs), and most patients achieve their genetic diagnosis through Multiplex Ligation-dependent Probe Amplification (MLPA) or exome sequencing. Here, we investigated a female patient presenting with muscular dystrophy who remained genetically undiagnosed after MLPA and exome sequencing. RNA sequencing (RNAseq) from the patient’s muscle biopsy identified an 85% reduction in DMD expression compared to 116 muscle samples included in the cohort. A de novo balanced translocation between chromosome 17 and the X chromosome (t(X;17)(p21.1;q23.2)) disrupting the DMD and BCAS3 genes was identified through trio whole genome sequencing (WGS). The combined analysis of RNAseq and WGS played a crucial role in the detection and characterisation of the disease-causing variant in this patient, who had been undiagnosed for over two decades. This case illustrates the diagnostic odyssey of female DMD patients with complex structural variants that are not detected by current panel or exome sequencing analysis.
Author(s): Segarra-Casas A, Yepez VA, Demidov G, Laurie S, Esteve-Codina A, Gagneur J, Parkhurst Y, Muni-Lofra R, Harris E, Marini-Bettolo C, Straub V, Topf A
Publication type: Article
Publication status: Published
Journal: International Journal of Molecular Sciences
Year: 2024
Volume: 25
Issue: 14
Online publication date: 16/07/2024
Acceptance date: 11/07/2024
Date deposited: 06/08/2024
ISSN (print): 1661-6596
ISSN (electronic): 1422-0067
Publisher: MDPI
URL: https://doi.org/10.3390/ijms25147793
DOI: 10.3390/ijms25147793
Data Access Statement: Further details and data are available upon request from the corresponding author.
PubMed id: 39063034
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