Academic Journal
Exome Sequencing and Optical Genome Mapping in Molecularly Unsolved Cases of Duchenne Muscular Dystrophy: Identification of a Causative X-Chromosomal Inversion Disrupting the DMD Gene
| العنوان: | Exome Sequencing and Optical Genome Mapping in Molecularly Unsolved Cases of Duchenne Muscular Dystrophy: Identification of a Causative X-Chromosomal Inversion Disrupting the DMD Gene |
|---|---|
| المؤلفون: | Leoni S. Erbe, Sabine Hoffjan, Sören Janßen, Moritz Kneifel, Karsten Krause, Wanda M. Gerding, Kristina Döring, Anne-Katrin Güttsches, Andreas Roos, Elena Buena Atienza, Caspar Gross, Thomas Lücke, Hoa Huu Phuc Nguyen, Matthias Vorgerd, Cornelia Köhler |
| المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 14716, p 14716 (2023) |
| بيانات النشر: | MDPI AG |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Duchenne muscular dystrophy, DMD, optical genome mapping, OGM, long-read sequencing, inversion, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that mainly affects boys due to X-linked recessive inheritance. In most affected individuals, MLPA or sequencing-based techniques detect deletions, duplications, or point mutations in the dystrophin-encoding DMD gene. However, in a small subset of patients clinically diagnosed with DMD, the molecular cause is not identified with these routine methods. Evaluation of the 60 DMD patients in our center revealed three cases without a known genetic cause. DNA samples of these patients were analyzed using whole-exome sequencing (WES) and, if unconclusive, optical genome mapping (OGM). WES led to a diagnosis in two cases: one patient was found to carry a splice mutation in the DMD gene that had not been identified during previous Sanger sequencing. In the second patient, we detected two variants in the fukutin gene ( FKTN ) that were presumed to be disease-causing. In the third patient, WES was unremarkable, but OGM identified an inversion disrupting the DMD gene (~1.28 Mb) that was subsequently confirmed with long-read sequencing. These results highlight the importance of reanalyzing unsolved cases using WES and demonstrate that OGM is a useful method for identifying large structural variants in cases with unremarkable exome sequencing. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/24/19/14716; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067; https://doaj.org/article/3ec8e1bd14f54769a046f4c0a9412e16 |
| DOI: | 10.3390/ijms241914716 |
| الاتاحة: | https://doi.org/10.3390/ijms241914716 https://doaj.org/article/3ec8e1bd14f54769a046f4c0a9412e16 |
| رقم الانضمام: | edsbas.C7C796D5 |
| قاعدة البيانات: | BASE |
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