Whole-Genome Sequencing Identified New Structural Variations in the

DMD Duchenne muscular dystrophy WGS X-inactivation structural variants translocation whole-genome sequencing

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
01 Sep 2023
Historique:
received: 07 08 2023
revised: 28 08 2023
accepted: 29 08 2023
medline: 11 9 2023
pubmed: 9 9 2023
entrez: 9 9 2023
Statut: epublish

Résumé

Dystrophinopathies are the most common muscle diseases, especially in men. In women, on the other hand, a manifestation of Duchenne muscular dystrophy is rare due to X-chromosomal inheritance. We present two young girls with severe muscle weakness, muscular dystrophies, and creatine kinase (CK) levels exceeding 10,000 U/L. In the skeletal muscle tissues, dystrophin staining reaction showed mosaicism. The almost entirely skewed X-inactivation in both cases supported the possibility of a dystrophinopathy. Despite standard molecular diagnostics (including multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS) gene panel sequencing), the genetic cause of the girls' conditions remained unknown. However, whole-genome sequencing revealed two reciprocal translocations between their X chromosomes and chromosome 5 and chromosome 19, respectively. In both cases, the breakpoints on the X chromosomes were located directly within the

Identifiants

pubmed: 37686372
pii: ijms241713567
doi: 10.3390/ijms241713567
pmc: PMC10488134
pii:
doi:

Substances chimiques

DMD protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Deutsche Forschungsgemeinschaft
ID : 444748124

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Auteurs

Natalie Pluta (N)

Department of Human Genetics, University of Würzburg, 97074 Würzburg, Germany.

Arpad von Moers (A)

Department of Pediatrics and Neuropediatrics, DRK Kliniken Berlin, 14050 Berlin, Germany.

Astrid Pechmann (A)

Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

Werner Stenzel (W)

Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117 Berlin, Germany.

Hans-Hilmar Goebel (HH)

Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117 Berlin, Germany.

David Atlan (D)

Phenosystems SA, 1807 Blonay, Switzerland.

Beat Wolf (B)

iCoSys, University of Applied Sciences Western Switzerland, 1700 Fribourg, Switzerland.

Indrajit Nanda (I)

Department of Human Genetics, University of Würzburg, 97074 Würzburg, Germany.

Ann-Kathrin Zaum (AK)

Department of Human Genetics, University of Würzburg, 97074 Würzburg, Germany.

Simone Rost (S)

Department of Human Genetics, University of Würzburg, 97074 Würzburg, Germany.
Medical Genetics Center (MGZ), 80335 Munich, Germany.

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Classifications MeSH