International Journal of Hematology

, Volume 103, Issue 3, pp 283–291 | Cite as

Genetic variations in complement factors in patients with congenital thrombotic thrombocytopenic purpura with renal insufficiency

  • Xinping Fan
  • Johanna A. Kremer Hovinga
  • Hiroko Shirotani-Ikejima
  • Yuka Eura
  • Hidenori Hirai
  • Shigenori Honda
  • Koichi Kokame
  • Magnus Mansouri Taleghani
  • Anne-Sophie von Krogh
  • Yoko Yoshida
  • Yoshihiro Fujimura
  • Bernhard Lämmle
  • Toshiyuki Miyata
Original Article


The congenital form of thrombotic thrombocytopenic purpura (TTP) is caused by genetic mutations in ADAMTS13. Some, but not all, congenital TTP patients manifest renal insufficiency in addition to microangiopathic hemolysis and thrombocytopenia. We included 32 congenital TTP patients in the present study, which was designed to assess whether congenital TTP patients with renal insufficiency have predisposing mutations in complement regulatory genes, as found in many patients with atypical hemolytic uremic syndrome (aHUS). In 13 patients with severe renal insufficiency, six candidate complement or complement regulatory genes were sequenced and 11 missense mutations were identified. One of these missense mutations, C3:p.K155Q mutation, is a rare mutation located in the macroglobulin-like 2 domain of C3, where other mutations predisposing for aHUS cluster. Several of the common missense mutations identified in our study have been reported to increase disease-risk for aHUS, but were not more common in patients with as compared to those without renal insufficiency. Taken together, our results show that the majority of the congenital TTP patients with renal insufficiency studied do not carry rare genetic mutations in complement or complement regulatory genes.


Atypical hemolytic uremic syndrome Complement factors Renal insufficiency Thrombotic thrombocytopenic purpura Upshaw–Schulman syndrome 


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Copyright information

© The Japanese Society of Hematology 2016

Authors and Affiliations

  • Xinping Fan
    • 1
    • 6
  • Johanna A. Kremer Hovinga
    • 2
  • Hiroko Shirotani-Ikejima
    • 1
  • Yuka Eura
    • 1
  • Hidenori Hirai
    • 1
  • Shigenori Honda
    • 1
  • Koichi Kokame
    • 1
  • Magnus Mansouri Taleghani
    • 2
  • Anne-Sophie von Krogh
    • 3
    • 4
  • Yoko Yoshida
    • 5
  • Yoshihiro Fujimura
    • 5
  • Bernhard Lämmle
    • 2
    • 7
  • Toshiyuki Miyata
    • 1
    • 8
  1. 1.Department of Molecular PathogenesisNational Cerebral and Cardiovascular CenterSuitaJapan
  2. 2.Department of Hematology and Central Hematology Laboratory, InselspitalBern University Hospital and University of BernBernSwitzerland
  3. 3.Department of Cancer Research and Molecular MedicineNorwegian University of Science and TechnologyTrondheimNorway
  4. 4.Department of HematologySt Olavs Hospital Trondheim University HospitalTrondheimNorway
  5. 5.Department of Blood Transfusion MedicineNara Medical UniversityKashiharaJapan
  6. 6.Department of Clinical LaboratoryBeijing Chaoyang Hospital, Capital Medical UniversityBeijingChina
  7. 7.Center for Thrombosis and Hemostasis (CTH)University Medical Center MainzMainzGermany
  8. 8.Department of Cerebrovascular MedicineNational Cerebral and Cardiovascular CenterSuitaJapan

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