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

Int J Hematol. 2016 Mar;103(3):283-91. doi: 10.1007/s12185-015-1933-7. Epub 2016 Feb 1.


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.

Trial registration: NCT01257269.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS13 Protein / genetics
  • Adult
  • Atypical Hemolytic Uremic Syndrome / genetics
  • Complement C3 / genetics*
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Purpura, Thrombotic Thrombocytopenic / congenital*
  • Purpura, Thrombotic Thrombocytopenic / genetics*
  • Renal Insufficiency / etiology*
  • Renal Insufficiency / genetics*


  • Complement C3
  • ADAMTS13 Protein
  • ADAMTS13 protein, human

Associated data