Genetic disorders in complement (regulating) genes in patients with atypical haemolytic uraemic syndrome (aHUS).
Westra, Dineke 1; Volokhina, Elena 1; van der Heijden, Eefje 1; Vos, Annemieke 2; Huigen, Marleen 2; Jansen, Jitske 2; van Kaauwen, Edwin 2; van der Velden, Thea 1; van de Kar, Nicole 1; van den Heuvel, Lambert 1,2,3
[Article]
Nephrology Dialysis Transplantation.
25(7):2195-2202, July 2010.
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Background. Atypical HUS (aHUS) is thought to be caused by predisposing mutations in genes encoding complement (regulating) proteins, such as Factor H (CFH), Factor I (IF), membrane co-factor protein (MCP) and Factor B (FB), or by auto-antibodies against CFH ([alpha]FH) in combination with a homozygous polymorphic deletion of the genes encoding Complement Factor H-related 1 and 3 ([DELTA]CFHR1/3). The clinical impact of this knowledge is high, as it might be a prognostic factor for the outcome of renal transplantations and kidney donations.
Methods. Mutational screening, by means of PCR and DNA sequencing, is performed in the above-mentioned genes in a group of 72 aHUS patients. Also, the presence of [alpha]FH and [DELTA]CFHR1/3 was tested in patients and controls.
Results. In 23 patients, a genetic aberration in at least one gene or the presence of [alpha]FH was found. A heterozygous mutation was observed in CFH in nine patients, in IF in seven patients and in MCP in three patients. No mutations were observed in FB. Seven patients presented [alpha]FH, of whom five also carried [DELTA]CFHR1/3. Three patients carried a combined mutation (two patients: IF and MCP; one patient: IF, [alpha]FH and [DELTA]CFHR1/3). A significant difference between patients and controls was detected for the presence of all three associated polymorphisms in CFH.
Conclusions. Genetic abnormalities or the presence of [alpha]FH were detected in 31.9% of the aHUS patients. Furthermore, bigenic mutations were present, indicating that routine DNA mutation analysis of all complement factors associated with aHUS is important.
(C) European Renal Association - European Dialysis and Transplant Association 2010. Published by Oxford University Press. All rights reserved.