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Lookup NU author(s): Professor Kevin MarchbankORCiD,
Professor Tim Goodship
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Atypical hemolytic uremic syndrome (aHUS) is associated with mutations in the gene CFH encoding the complement regulator factor H (CFH). We previously reported a family, in which three individuals had partial CFH deficiency but only one was affected by aHUS. We have investigated this family further to show that the partial CFH deficiency is associated with a heterozygous CFH mutation (c.2768T>G, p.Tyr899Asp). We used the polymorphic CFH variant p.His402Tyr to track expression of p.Tyr899Asp, and found that this mutant was expressed in minimal quantities in serum. In the one affected individual we found a second CFH mutation (c.3581G>A, p.Gly1194Asp) on the other allele which was expressed normally. We showed that this mutant, which has been described previously in aHUS, has impaired regulation of cell surface complement activation. The affected individual in this family is therefore a compound heterozygote for two functionally significant CFH mutations. Two individuals (mother and male sib) in the pedigree carried only c.2768T>G, p.Tyr899Asp and one (father) carried only c.3581G>A, p.Gly1194Asp, and all three were asymptomatic. Thus, further investigation of this family has enabled us to clarify the genotype-phenotype correlation. (C) 2010 Published by Elsevier Ltd.
Author(s): Johnson SA, Williams JM, Hakobyan S, Richards A, Perkins SJ, Marchbank KJ, Goodship THJ, Morgan BP, Taylor CM, Savage COS
Publication type: Article
Publication status: Published
Journal: Molecular Immunology
Print publication date: 01/04/2010
ISSN (print): 0161-5890
ISSN (electronic): 1872-9142
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