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Two different clinical phenotypes of Creutzfeldt-Jakob disease with a M232R substitution

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Abstract

Objective

To describe the clinical features of Creutzfeldt-Jakob disease with a substitution of arginine for methionine (M232R substitution) at codon 232 (CJD232) of the prion protein gene (PRNP).

Patients and methods

We evaluated the clinical and laboratory features of 20 CJD232 patients: age of onset, initial symptoms, duration until becoming akinetic and mute, duration until occurrence of periodic sharp and wave complexes on EEG (PSWC), MRI findings, and the presence of CSF 14-3-3 protein. Immunohistochemically, prion protein (PrP) deposition was studied.

Results

None of the patients had a family history of CJD. We recognized two clinical phenotypes: a rapidly progressive type (rapidtype) and a slowly progressive type (slow-type). Out of 20 patients, 15 became akinetic and mute, demonstrated myoclonus, and showed PSWC within a mean duration of 3.1, 2.4, and 2.8 months, respectively (rapid-type). Five showed slowly progressive clinical courses (slow-type). Five became akinetic and mute and four demonstrated myoclonus within a mean duration of 20.6 and 15.3 months, respectively, which were significantly longer than those in the rapid-type. Only one demonstrated PSWC 13 months after the onset. Diffuse synaptic-type deposition was demonstrated in four rapidtype patients, and perivacuolar and diffuse synaptic-type deposition in two, and diffuse synaptic-type deposition in one slow-type patient. Three of 50 suspected but non-CJD patients had the M232R substitution.

Conclusions

Patients with CJD232 had no family history like patients with sCJD, and showed two different clinical phenotypes in spite of having the same PRNP genotype. More studies are needed to determine whether M232R substitution causes the disease and influences the disease progression.

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Author information

Authors and Affiliations

  1. Dept. of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi,Aoba-ku, Sendai, 980-8574, Japan

    Y. Shiga* MD, PhD, S. Kanno MD, I. Nakashima MD, PhD, K. Fujihara MD,PhD & Y. Itoyama MD, PhD

  2. The First Department of Internal Medicine, Graduate School of Medicine, Nagasaki University, Japan

    K. Satoh MD, PhD

  3. Division of CJD Science and Technology, Graduate School of Medicine, Tohoku University, Japan

    T. Kitamoto* MD, PhD

  4. Dept. of Neurology, Kohnan Hospital, Japan

    S. Sato MD, PhD

  5. Dept. of Neurology, Minami Okayama National Hospital, Japan

    H. Takata MD, PhD & K. Nobukuni MD, PhD

  6. Dept. of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan

    S. Kuroda* MD, PhD

  7. Dept. of Neurology, Brain Research Institute, Niigata University, Japan

    H. Takano MD, PhD & Y. Umeda MD, PhD

  8. Dept. of Neurology, Nishitaga National Hospital, Japan

    H. Konno MD, PhD

  9. Dept. of Neurology, Isahaya General Hospital, Japan

    K. Nagasato MD, PhD

  10. Dept. of Neurology, Nagasaki Kita Hospital, Japan

    A. Satoh MD, PhD

  11. Dept. of Neuropsychiatry, Graduate School of Medicine, Yamaguchi University, Japan

    Y. Matsuda MD, PhD

  12. Yokohama Miyazaki Hospital of Neurosurgery, Japan

    M. Hidaka MD, PhD

  13. Dept. of Neurology, Matsudo Municipal Hospital, Japan

    H. Takahashi MD, PhD

  14. Dept. of Neurology, Graduate School of Medicine, Yamaguchi University, Japan

    Y. Sano MD, PhD

  15. Dept. of Neurology, Shizuoka General Hospital, Japan

    K. Kim MD, PhD

  16. Dept. of Neurology, Shizuoka National Medical Center, Japan

    T. Konishi MD, PhD

  17. Division of Prion Protein Biology, Graduate School of Medicine, Tohoku University, Japan

    K. Doh-ura MD, PhD

  18. National Center for Neurology and Psychiatry, Kohnodai Hospital, Japan

    T. Sato* MD, PhD

  19. Dept. of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Japan

    K. Sasaki MD, PhD

  20. Dept. of Public Health, Jichi Medical School, Japan

    Y. Nakamura* MD, PhD

  21. Depts. of Neurology and Neurobiology of Aging, Graduate School of Medical Science, Kanazawa University, Japan

    M. Yamada* MD, PhD

  22. Dept. of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Japan

    H. Mizusawa* MD, PhD

Authors
  1. Y. Shiga* MD, PhD
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  2. K. Satoh MD, PhD
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  3. T. Kitamoto* MD, PhD
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  4. S. Kanno MD
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  5. I. Nakashima MD, PhD
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  6. S. Sato MD, PhD
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  7. K. Fujihara MD,PhD
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  8. H. Takata MD, PhD
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  9. K. Nobukuni MD, PhD
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  10. S. Kuroda* MD, PhD
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  11. H. Takano MD, PhD
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  12. Y. Umeda MD, PhD
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  13. H. Konno MD, PhD
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  14. K. Nagasato MD, PhD
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  15. A. Satoh MD, PhD
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  16. Y. Matsuda MD, PhD
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  17. M. Hidaka MD, PhD
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  18. H. Takahashi MD, PhD
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  19. Y. Sano MD, PhD
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  20. K. Kim MD, PhD
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  21. T. Konishi MD, PhD
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  22. K. Doh-ura MD, PhD
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  23. T. Sato* MD, PhD
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  24. K. Sasaki MD, PhD
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  25. Y. Nakamura* MD, PhD
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  26. M. Yamada* MD, PhD
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  27. H. Mizusawa* MD, PhD
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  28. Y. Itoyama MD, PhD
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Corresponding author

Correspondence to Y. Shiga* MD, PhD.

Additional information

* The Creutzfeldt-Jakob Disease Surveillance Committee, Japan.

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Shiga*, Y., Satoh, K., Kitamoto*, T. et al. Two different clinical phenotypes of Creutzfeldt-Jakob disease with a M232R substitution. J Neurol 254, 1509–1517 (2007). https://doi.org/10.1007/s00415-007-0540-9

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  • DOI: https://doi.org/10.1007/s00415-007-0540-9

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