Novel Sequence Variation Affects GPIbÃÂ± in Post-diarrheal Hemolytic Uremic Syndrome
- *Corresponding Author:
- van den Heuvel L.P
Department of Pediatric Nephrology
(774) Radboud University Nijmegen Medical Center
P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
E-mail: [email protected]
Received Date: February 04, 2014; Accepted Date: March 22, 2014; Published Date: March 27, 2014
Citation: Volokhina E, Jakobi A, Urbanus R, Huizinga E, Sluiter H, et al. (2014) Novel Sequence Variation Affects GPIb α in Post-diarrheal Hemolytic Uremic Syndrome. J Nephrol Therapeutic S11:007. doi:10.4172/2161-0959.S11-007
Copyright: © 2014 Volokhina E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.