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Analysis of patients with atypical hemolytic uremic syndrome treated at the Mie University Hospital: concentration of C3 p.I1157T mutation

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Abstract

Atypical hemolytic uremic syndrome (aHUS) is caused by abnormalities of the complement system and has a significantly poor prognosis. The clinical phenotypes of 12 patients in nine families with aHUS with familial or recurrent onset and ADAMTS13 activity of ≥20 % treated at the Mie University Hospital were examined. In seven of the patients, the first episode of aHUS occurred during childhood and ten patients experienced a relapse. All patients had renal dysfunction and three had been treated with hemodialysis. Seven patients experienced probable triggering events including common cold, influenza, bacterial infection and/or vaccination for influenza. All patients had entered remission, and renal function was improved in 11 patients. DNA sequencing of six candidate genes, identified a C3 p.I1157T missense mutation in all eight patients in six families examined and this mutation was causative for aHUS. A causative mutation THBD p.D486Y was also identified in an aHUS patient. Four missense mutations, CFH p.V837I, p.Y1058H, p.V1060L and THBD p.R403K may predispose to aHUS manifestation; the remaining seven missense mutations were likely neutral. In conclusion, the clinical phenotypes of aHUS are various, and there are often trigger factors. The C3 p.I1157T mutation was identified as the causative mutation for aHUS in all patients examined, and may be geographically concentrated in or around the Mie prefecture in central Japan.

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Acknowledgments

This work was supported in part by a Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan for Blood Coagulation Abnormalities, the Ministry of Education, Culture, Sports, Science and Technology of Japan, grant from the Uehara Memorial Foundation and grant from the Takeda Science Foundation.

Conflict of interest

All authors have no conflict of interest to report.

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Authors and Affiliations

  1. Blood Transfusion Service, Mie University Hospital, Tsu, Japan

    Takeshi Matsumoto & Kohshi Ohishi

  2. Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan

    Xinping Fan & Toshiyuki Miyata

  3. Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan

    Eiji Ishikawa & Masaaki Ito

  4. Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan

    Keishirou Amano, Hidemi Toyoda & Yoshihiro Komada

  5. Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan

    Naoyuki Katayama

  6. Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan

    Yoko Yoshida, Masanori Matsumoto & Yoshihiro Fujimura

  7. Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, Tsu, Japan

    Makoto Ikejiri & Hideo Wada

  8. Department of Laboratory Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Hideo Wada

Authors
  1. Takeshi Matsumoto
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  2. Xinping Fan
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  3. Eiji Ishikawa
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  4. Masaaki Ito
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  5. Keishirou Amano
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  6. Hidemi Toyoda
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  7. Yoshihiro Komada
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  8. Kohshi Ohishi
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  9. Naoyuki Katayama
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  10. Yoko Yoshida
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  11. Masanori Matsumoto
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  12. Yoshihiro Fujimura
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  13. Makoto Ikejiri
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  14. Hideo Wada
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  15. Toshiyuki Miyata
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Corresponding author

Correspondence to Hideo Wada.

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Matsumoto, T., Fan, X., Ishikawa, E. et al. Analysis of patients with atypical hemolytic uremic syndrome treated at the Mie University Hospital: concentration of C3 p.I1157T mutation. Int J Hematol 100, 437–442 (2014). https://doi.org/10.1007/s12185-014-1655-2

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  • DOI: https://doi.org/10.1007/s12185-014-1655-2

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