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Segarra-Casas, A.* ; Yépez, V.A.* ; Demidov, G.* ; Laurie, S.* ; Esteve-Codina, A.* ; Gagneur, J. ; Parkhurst, Y.* ; Muni-Lofra, R.* ; Harris, E.* ; Marini-Bettolo, C.* ; Straub, V.* ; Töpf, A.*

An integrated transcriptomics and genomics approach detects an X/Autosome translocation in a female with duchenne muscular dystrophy.

Int. J. Mol. Sci. 25:7793 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Dmd ; Duchenne Muscular Dystrophy ; Rna Sequencing ; Female Carrier ; Genetic Diagnosis ; Translocation ; Whole Genome Sequencing; Joint Consensus Recommendation; Manifesting Carriers; Structural Variants; Medical Genetics; American-college; Sequence; Database; Chromosome; Standards; Complex
ISSN (print) / ISBN 1422-0067
e-ISSN 1661-6596
Zeitschrift International Journal of Molecular Sciences
Quellenangaben Band: 25, Heft: 14, Seiten: , Artikelnummer: 7793 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen Ministerio de Universidades
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
European Union