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De novo mutation in DMD gene in a patient with combined hemophilia A and Duchenne muscular dystrophy

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Abstract

We report an unusual case of a patient with two combined X-linked diseases, severe hemophilia A (HA) and Duchenne muscular dystrophy (DMD), of which only HA was hereditary. There was no family history of muscular dystrophy. Genetic analysis revealed that HA was caused by the hereditary coagulation factor VIII (F8) intron 22 inversion (distal/type I inversion), whereas DMD was caused by a de novo deletion in the dystrophin gene. This is the first report of a patient with two severe X-linked diseases, of which only HA was hereditary. Despite the fact that the probability of acquiring two X-linked abnormalities, one hereditary and one de novo, is extremely low, the emergence of such cases indicates that genetic testing for distinct X-linked diseases could be of importance in patients with hereditary hemophilia.

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Fig. 1
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Abbreviations

APCC:

Activated prothrombin complex concentrates

CK:

Creatine kinase

DMD:

Duchenne muscular dystrophy

DMD gene:

Dystrophin gene

HA:

Hemophilia A

PCC:

Prothrombin complex concentrates

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Acknowledgments

This work was supported by the grant J1-8762 provided by the Slovenian Research Agency to RK and LS. The authors would like to thank Dr. Gian Antonio Danieli and Dr. Maurizio Rosa for their contributions to molecular analysis of DMD gene. We also thank Dr. Jane Gitschier, Howard Hughes Medical Institute, University of California, San Francisco, for kindly supplying the plasmid p482.6 probe.

Ethical standard

The study was approved by the National Medical Ethics Committee of the Republic of Slovenia. The patient and the family members were informed about the purpose, procedures, meaning, limitations and possible consequences of these genetic analyses by the treating physician and signed consent was obtained.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Oxford, Oxford, UK

    Lana Strmecki

  2. Faculty of Medicine, Medical Centre for Molecular Biology, Institute of Biochemistry, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia

    Lana Strmecki, Petra Hudler & Radovan Komel

  3. Department of Paediatrics, National Haemophilia Centre, University Medical Centre, Ljubljana, Slovenia

    Majda Benedik-Dolničar

Authors
  1. Lana Strmecki
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  2. Petra Hudler
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  3. Majda Benedik-Dolničar
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  4. Radovan Komel
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Corresponding authors

Correspondence to Petra Hudler or Radovan Komel.

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Strmecki, L., Hudler, P., Benedik-Dolničar, M. et al. De novo mutation in DMD gene in a patient with combined hemophilia A and Duchenne muscular dystrophy. Int J Hematol 99, 184–187 (2014). https://doi.org/10.1007/s12185-013-1488-4

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  • DOI: https://doi.org/10.1007/s12185-013-1488-4

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