title: The complement factor H R1210C mutation is associated with atypical hemolytic uremic syndrome.
abstract: Mutations in the gene encoding complement factor H (CFH) that alter the C3b/polyanions-binding site in the C-terminal region impair the capacity of factor H to protect host cells. These mutations are also strongly associated with atypical hemolytic uremic syndrome (aHUS). Although most of the aHUS-associated CFH mutations seem "unique" to an individual patient or family, the R1210C mutation has been reported in several unrelated aHUS patients from distinct geographic origins. Five aHUS pedigrees and 7 individual aHUS patients were analyzed to identify potential correlations between the R1210C mutation and clinical phenotype and to characterize the origins of this mutation. The clinical phenotype of aHUS patients carrying the R1210C mutation was heterogeneous. Interestingly, 12 of the 13 affected patients carried at least one additional known genetic risk factor for aHUS. These data are in accord with the 30% penetrance of aHUS in R1210C mutation carriers, as it seems that the presence of other genetic or environmental risk factors significantly contribute to the manifestation and severity of aHUS in these subjects. Genotype analysis of CFH and CFHR3 polymorphisms in the 12 unrelated carriers suggested that the R1210C mutation has a single origin. In conclusion, the R1210C mutation of complement factor H is a prototypical aHUS mutation that is present as a rare polymorphism in geographically separated human populations.
authors.affiliation: Centro de Investigaciones Biológicas, Ramiro de Maeztu 9, 28040 Madrid, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Martinez-Barricarte
authors.forename: Gaia
authors.initials: G
authors.lastname: Pianetti
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gautard
authors.forename: Joachim
authors.initials: J
authors.lastname: Misselwitz
authors.forename: Lisa
authors.initials: L
authors.lastname: Strain
authors.forename: Veronique
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.forename: Christine
authors.initials: C
authors.lastname: Skerka
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: Tim
authors.initials: T
authors.lastname: Goodship
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Santiago Rodriguez
authors.initials: SR
authors.lastname: de Cordoba
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017242:Complement Factor H / Q000235:genetics*; D017244:Complement Factor I / Q000235:genetics; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D051916:Membrane Cofactor Protein / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: D051916:Membrane Cofactor Protein; D017242:Complement Factor H; C493611:CFI protein, human; D017244:Complement Factor I