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

International Journal of Hematology
Xinping FanToshiyuki Miyata

Abstract

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 comp...Continue Reading

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Citations

May 20, 2016·International Journal of Hematology·Toshiyuki MiyataMasaomi Nangaku
Oct 6, 2017·Indian Journal of Gastroenterology : Official Journal of the Indian Society of Gastroenterology·Ashish GoelChundamannil E Eapen
Jan 23, 2018·Journal of Thrombosis and Haemostasis : JTH·J A Kremer HovingaM Schaller
Apr 7, 2017·Nature Reviews. Disease Primers·Johanna A Kremer HovingaKaren Vanhoorelbeke

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