Balanced Translocations Involving the DMD Gene as a Cause of Muscular Dystrophy in Female Children: A Description of Three Cases
Duchenne muscular dystrophy (DMD) is typically described in boys with a pathogenic variant in the <i>DMD</i>. However, in certain cases, females may also exhibit symptoms of this X-linked disorder. In the present study, the cause of Duchenne muscular dystrophy in three girls was reciprocal translocations t(X;2), t(X;12), and t(X;16), with breakpoints located within the <i>DMD</i> gene sequence. All patients had global development delay, predominantly proximal muscle weakness, calf muscle hypertrophy, and elevated creatine kinase levels up to 100 times the normal range (16,000-26,694 U/L). All underwent cardiac ultrasound and electromyography, and two of the girls also had muscle MRI data. After receiving negative results of MLPA aimed at the detection of <i>DMD</i> deletions and duplications, as well as the limb-girdle muscular dystrophy gene panel sequencing, the patients were referred to whole genome sequencing, which allowed to detect a translocation involving the short arm of the X chromosome and with breakpoints in the <i>DMD</i>. Karyotyping confirmed reciprocal translocations in all patients, with de novo status established in all three cases. The results of this study contribute to the understanding of clinical polymorphism and genetic heterogeneity of the disease, highlighting the importance of a comprehensive approach to genetic diagnostics in atypical cases.
Authors
- Andrey V. Marakhonov (ORCID: https://orcid.org/0000-0002-0972-5118)
- Mariya Antonova (ORCID: https://orcid.org/0009-0006-7684-6434)
- Elena Zinina (ORCID: https://orcid.org/0000-0001-5017-7996)
- Aysylu F. Murtazina (ORCID: https://orcid.org/0000-0001-7023-7378)
- V. A. Bulanova (ORCID: https://orcid.org/0000-0002-9333-3271)
- Olga Shchagina (ORCID: https://orcid.org/0000-0003-4905-1303)
- И. В. Шаркова (ORCID: https://orcid.org/0000-0002-5819-4835)
- Е. Л. Дадали (ORCID: https://orcid.org/0000-0001-5602-2805)
- Yulia M. Suvorova (ORCID: https://orcid.org/0000-0001-9758-8178)
- E. О. Vorontsova (ORCID: https://orcid.org/0000-0003-2291-6485)
- Д. О. Казаков (ORCID: https://orcid.org/0000-0003-3071-578X)
- Svetlana A. Repina (ORCID: https://orcid.org/0000-0001-5244-3901)
- Nina Demina (ORCID: https://orcid.org/0000-0003-0724-9004)
- A. V. Polyakov (ORCID: https://orcid.org/0000-0002-0105-1833)
- D. Vlodavets (ORCID: https://orcid.org/0000-0003-2635-2752)
- Maria Sumina (ORCID: https://orcid.org/0000-0002-2883-4029)
- Sergey I. Kutsev (ORCID: https://orcid.org/0000-0002-3133-8018)
- Н.В. Шилова (ORCID: https://orcid.org/0000-0002-0641-1084)
- Olga A. Rybakova
Institutions
- Yaroslavl State Medical Academy (RU)
- Pirogov Russian National Research Medical University (RU)
- 490 BioTech (United States) (US)
- Research Centre for Medical Genetics (RU)
- Ural Institute of Cardiology (RU)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-09-25
- DOI
- https://doi.org/10.3390/ijms26199389
- Citations
- 1
- Primary Topic
- Muscle Physiology and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.81