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An Integrated Transcriptomics and Genomics Approach Detects an X/Autosome Translocation in a Female with Duchenne Muscular Dystrophy
by
Alba Segarra-Casas
Alba Segarra-Casas
,
Vicente A. Yépez
Vicente A. Yépez
German Demidov
German Demidov
Steven Laurie
Steven Laurie
Anna Esteve-Codina
Anna Esteve-Codina
Julien Gagneur
Julien Gagneur
Dr. Julien Gagneur studied Applied Mathematics at École Centrale Paris and Machine Learning at the [...]
Dr. Julien Gagneur studied Applied Mathematics at École Centrale Paris and Machine Learning at the École Normale Supérieure de Cachan (France). He received his Ph.D. in Applied Mathematics in 2004 from the École Centrale Paris (France) for his work performed in the Heidelberg-based biotech companies Lion Bioscience and Cellzome AG. Professor Gagneur then joined the Genome Biology department of the European Molecular Biology Laboratory (EMBL) in Heidelberg. He assumed a group leader position at the Gene Center of the Ludwig-Maximilians-Universität in Munich in 2012. In 2016, he accepted an appointment as assistant professor for Computational Biology at the TUM. Since 2020, he has been a full professor at the TUM. His research focuses on delineating the genetic basis of gene regulation and its implication in diseases.
Yolande Parkhurst
Yolande Parkhurst
Robert Muni-Lofra
Robert Muni-Lofra
Elizabeth Harris
Elizabeth Harris
Chiara Marini-Bettolo
Chiara Marini-Bettolo
Dr. Chiara Marini-Bettolo is a consultant neurologist and is the clinical lead of the Highly Service [...]
Dr. Chiara Marini-Bettolo is a consultant neurologist and is the clinical lead of the Highly Specialised Service for Limb-Girdle Muscular Dystrophies (LGMDs). Chiara completed her medical degree and training in Neurology at the University of Rome Sapienza and has always had a special interest in neuromuscular disorders. During her training in Neurology, she was awarded a Scientific Fellowship by the European Federation of Neurological Societies, which gave her the opportunity to join the Neuromuscular team at Imperial College London, working on a lab-based project on inflammatory myopathies. In 2015, she completed her Ph.D. in neuromuscular disorders at Imperial College London. Since joining the John Walton Muscular Dystrophy Centre at Newcastle University, Chiara has been leading the Clinical Team and the Highly Specialised Service for Limb-Girdle Muscular Dystrophies (LGMDs). She runs adult and paediatric neuromuscular clinics across the region and, more recently, has led the implementation of a novel treatment currently available under various access schemes in Newcastle. Chiara has a strong research interest and is the principal investigator for some of the patient registries curated at the JWMDRC.
Volker Straub
Volker Straub
Prof. Volker Straub is professor of Neuromuscular Genetics and the director of the John Walton at a [...]
Prof. Volker Straub is professor of Neuromuscular Genetics and the director of the John Walton Muscular Dystrophy Research Centre at Newcastle University, Newcastle upon Tyne, UK. Prof. Straub was trained as a paediatric neurologist at the University of Düsseldorf and the University of Essen in Germany. He wrote his Ph.D. thesis on Duchenne muscular dystrophy (DMD) and worked as a postdoctoral research fellow in Dr. Kevin Campbell’s laboratory at the Howard Hughes Medical Institute at the University of Iowa in Iowa City, USA. Prof. Straub has a long-standing interest in the pathogenesis of genetic muscle diseases.
Ana Töpf
Ana Töpf
Dr. Ana Töpf is a senior research associate at the John Walton Muscular Dystrophy Research Centre a [...]
Dr. Ana Töpf is a senior research associate at the John Walton Muscular Dystrophy Research Centre in the UK, where she leads the Next Generation Sequencing team. She obtained her Ph.D. in Biological Sciences from Durham University in 2003. She is a Molecular Biologist by training and has over 15 years of experience in the analysis and interpretation of omics data for rare diseases, particularly neuromuscular and neurodevelopmental conditions. Throughout her career in the NMD field, Dr. Töpf has co-authored +100 publications, including the discovery of new disease genes and pathomechanisms and, more recently, a novel digenic model for a congenital skeletal myopathy.
1
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 3BZ, UK
2
Genetics Department, Institut de Recerca Sant Pau (IR SANT PAU), Hospital de la Santa Creu i Sant Pau, Genetics and Microbiology Department, Universitat Autonoma de Barcelona, 08041 Barcelona, Spain
3
School of Computation, Information and Technology, Technical University of Munich, 85748 Garching, Germany
4
Universitätsklinikum Tübingen—Institut für Medizinische Genetik und angewandte Genomik, 72076 Tübingen, Germany
5
Centro Nacional de Análisis Genómico (CNAG), 08028 Barcelona, Spain
6
Universitat de Barcelona (UB), 08007 Barcelona, Spain
7
Institute of Human Genetics, School of Medicine, Technical University of Munich, 81675 Munich, Germany
8
Computational Health Center, Helmholtz Center Munich, 85764 Neuherberg, Germany
9
Muscle Immunoanalysis Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(14), 7793; https://doi.org/10.3390/ijms25147793 (registering DOI)
Submission received: 15 June 2024
/
Revised: 8 July 2024
/
Accepted: 11 July 2024
/
Published: 16 July 2024
Abstract
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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MDPI and ACS Style
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.;
et al. An Integrated Transcriptomics and Genomics Approach Detects an X/Autosome Translocation in a Female with Duchenne Muscular Dystrophy. Int. J. Mol. Sci. 2024, 25, 7793.
https://doi.org/10.3390/ijms25147793
AMA Style
Segarra-Casas A, Yépez VA, Demidov G, Laurie S, Esteve-Codina A, Gagneur J, Parkhurst Y, Muni-Lofra R, Harris E, Marini-Bettolo C,
et al. An Integrated Transcriptomics and Genomics Approach Detects an X/Autosome Translocation in a Female with Duchenne Muscular Dystrophy. International Journal of Molecular Sciences. 2024; 25(14):7793.
https://doi.org/10.3390/ijms25147793
Chicago/Turabian Style
Segarra-Casas, Alba, Vicente A. Yépez, German Demidov, Steven Laurie, Anna Esteve-Codina, Julien Gagneur, Yolande Parkhurst, Robert Muni-Lofra, Elizabeth Harris, Chiara Marini-Bettolo,
and et al. 2024. "An Integrated Transcriptomics and Genomics Approach Detects an X/Autosome Translocation in a Female with Duchenne Muscular Dystrophy" International Journal of Molecular Sciences 25, no. 14: 7793.
https://doi.org/10.3390/ijms25147793
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