Abstract
Background: Hemolytic uremic syndrome (HUS) is one of the major causes of renal failure in children. In most
cases the disease is caused by infection with Shiga toxin- producing Escherichia coli (STEC) and preceded by diarrhea.
Only in 15% of cases STEC infection leads to HUS. Genetic predisposition of a patient to develop HUS after STEC
infection might play a role, but very few reports on this subject are available. We describe a novel missense mutation
in the GP1BA gene encoding platelet-receptor glycoprotein Ibα (GPIbα) in a severely affected HUS patient.
Methods: GP1BA was screened by Sanger sequencing. Binding of recombinant GPIbα and von Willebrand factor
(VWF) fragments was analyzed using surface plasmon resonance (SPR). The hematological studies using patient
blood were performed.
Results: The detected heterozygous mutation p.Pro46Leu is located in the proximity to one of the two GPIbα-VWF
binding sites. SPR experiments show that the p.Pro46Leu leads to a small increase in GPIbα-VWF binding (p<0.001).
The hemostatic parameters of patient blood after recovery from HUS show normal values.
Conclusions: The described mutation affects GPIbα interaction with VWF in a mild gain-of-function manner and
might have contributed to a prothrombotic state in the patient and to development of HUS.
Original language | English |
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Article number | 007 |
Number of pages | 5 |
Journal | Journal of nephrology & therapeutics |
Volume | S11 |
DOIs | |
Publication status | Published - 2014 |