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 (alphaFH) in combination with a homozygous polymorphic deletion of the genes encoding Complement Factor H-related 1 and 3 (DeltaCFHR1/3). 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 alphaFH and DeltaCFHR1/3 was tested in patients and controls. RESULTS: In 23 patients, a genetic aberration in at least one gene or the presence of alphaFH 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 alphaFH, of whom five also carried DeltaCFHR1/3. Three patients carried a combined mutation (two patients: IF and MCP; one patient: IF, alphaFH and DeltaCFHR1/3). 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 alphaFH 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.
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 (alphaFH) in combination with a homozygous polymorphic deletion of the genes encoding Complement Factor H-related 1 and 3 (DeltaCFHR1/3). 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 alphaFH and DeltaCFHR1/3 was tested in patients and controls. RESULTS: In 23 patients, a genetic aberration in at least one gene or the presence of alphaFH 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 alphaFH, of whom five also carried DeltaCFHR1/3. Three patients carried a combined mutation (two patients: IF and MCP; one patient: IF, alphaFH and DeltaCFHR1/3). 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 alphaFH 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.
Authors: Sjoerd A M E G Timmermans; Myrurgia A Abdul-Hamid; Judith Potjewijd; Ruud O M F I H Theunissen; Jan G M C Damoiseaux; Chris P Reutelingsperger; Pieter van Paassen Journal: J Am Soc Nephrol Date: 2018-06-01 Impact factor: 10.121
Authors: Dana Provaznikova; Simon Rittich; Michal Malina; Tomas Seeman; Iuri Marinov; Magdalena Riedl; Ingrid Hrachovinova Journal: Pediatr Nephrol Date: 2011-06-27 Impact factor: 3.714
Authors: Stuart Cantsilieris; Bradley J Nelson; John Huddleston; Carl Baker; Lana Harshman; Kelsi Penewit; Katherine M Munson; Melanie Sorensen; AnneMarie E Welch; Vy Dang; Felix Grassmann; Andrea J Richardson; Robyn H Guymer; Tina A Graves-Lindsay; Richard K Wilson; Bernhard H F Weber; Paul N Baird; Rando Allikmets; Evan E Eichler Journal: Proc Natl Acad Sci U S A Date: 2018-04-23 Impact factor: 11.205
Authors: David N Cooper; Michael Krawczak; Constantin Polychronakos; Chris Tyler-Smith; Hildegard Kehrer-Sawatzki Journal: Hum Genet Date: 2013-07-03 Impact factor: 4.132