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Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population

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Abstract

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18–55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients’ blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

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Acknowledgments

During this study, AS was funded by Sigrid Jusélius Foundation, Jane and Aatos Erkko Foundation, European Research Council, University of Helsinki, and Academy of Finland. We are grateful to all study investigators and the core facility study team at the University of Rostock.

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Authors and Affiliations

  1. Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Per Dubbsgatan 14, POB 430, 40530, Gothenburg, Sweden

    Turgut Tatlisumak

  2. Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden

    Turgut Tatlisumak

  3. Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland

    Turgut Tatlisumak, Jukka Putaala, Tiina M. Metso, Sami Curtze & Anu Suomalainen

  4. Research Program for Molecular Neurology, University of Helsinki, Helsinki, Finland

    Markus Innilä & Anu Suomalainen

  5. Department of Neurology, Medical University of Graz, Graz, Austria

    Christian Enzinger & Franz Fazekas

  6. Department of Neurology, Ernst-Moritz-Arndt University Medicine, Greifswald, Germany

    Bettina von Sarnowski

  7. Department of Neurology, Unidade Cerebrovascular Hospital de São José, Lisbon, Portugal

    Alexandre Amaral-Silva

  8. Department of Neurology, Hospital Vila Franca de Xira, Vila Franca de Xira, Portugal

    Alexandre Amaral-Silva

  9. Department of Neurology, Charite University, Berlin, Germany

    Gerhard Jan Jungehulsing

  10. Department of Neurology, University of Giessen, Giessen, Germany

    Christian Tanislav

  11. Austin Health and Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, VIC, Australia

    Vincent Thijs

  12. Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany

    Arndt Rolfs

  13. Department of Clinical Neurosciences Neurology, Lund University, Lund, Sweden

    Bo Norrving

  14. Department of Neurology, New York University School of Medicine, New York, NY, USA

    Edwin H. Kolodny

Authors
  1. Turgut Tatlisumak
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  2. Jukka Putaala
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  3. Markus Innilä
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  4. Christian Enzinger
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  5. Tiina M. Metso
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  6. Sami Curtze
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  7. Bettina von Sarnowski
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  8. Alexandre Amaral-Silva
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  9. Gerhard Jan Jungehulsing
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  10. Christian Tanislav
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  11. Vincent Thijs
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  12. Arndt Rolfs
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  13. Bo Norrving
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  14. Franz Fazekas
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  15. Anu Suomalainen
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  16. Edwin H. Kolodny
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Corresponding author

Correspondence to Turgut Tatlisumak.

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Funding

The sifap1 study (http://www.sifap.eu/, NCT00414583) has been supported by an unrestricted scientific Grant from Shire Human Genetic Therapies to the University of Rostock.

Conflicts of interest

None.

Ethical standards

Ethics committee of the Medical Association Mecklenburg-Vorpommern (Board 2), University of Rostock, Rostock, Germany has approved this study on 14-SEPTEMBER-2006.

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Tatlisumak, T., Putaala, J., Innilä, M. et al. Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population. J Neurol 263, 257–262 (2016). https://doi.org/10.1007/s00415-015-7969-z

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  • DOI: https://doi.org/10.1007/s00415-015-7969-z

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