The complement factor H R1210C mutation is associated with atypical hemolytic uremic syndrome.
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.
Martinez-Barricarte
Ruben
R
Centro de Investigaciones Biológicas, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Pianetti
Gaia
G
Gautard
Ruxandra
R
Misselwitz
Joachim
J
Strain
Lisa
L
Fremeaux-Bacchi
Veronique
V
Skerka
Christine
C
Zipfel
Peter F
PF
Goodship
Tim
T
Noris
Marina
M
Remuzzi
Giuseppe
G
de Cordoba
Santiago Rodriguez
SR
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
D051916:Membrane Cofactor Protein; D017242:Complement Factor H; C493611:CFI protein, human; D017244:Complement Factor I