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

Fan, Xinping; Kremer Hovinga, Johanna Anna; Shirotani-Ikejima, Hiroko; Eura, Yuka; Hirai, Hidenori; Honda, Shigenori; Kokame, Koichi; Mansouri Taleghani, Magnus; von Krogh, Anne-Sophie; Yoshida, Yoko; Fujimura, Yoshihiro; Lämmle, Bernhard; Miyata, Toshiyuki (2016). Genetic variations in complement factors in patients with congenital thrombotic thrombocytopenic purpura with renal insufficiency. International journal of hematology, 103(3), pp. 283-291. Springer 10.1007/s12185-015-1933-7

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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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Kremer Hovinga, Johanna Anna; Mansouri Taleghani, Magnus and Lämmle, Bernhard


600 Technology > 610 Medicine & health








Verena Zwahlen

Date Deposited:

29 Mar 2016 10:31

Last Modified:

02 Feb 2017 02:30

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

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




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