RT Journal Article
T1 Variant-specific quantification of factor H in plasma identifies null alleles associated with atypical hemolytic uremic syndrome
A1 Hakobyan, Svetlana
A1 Tortajada Alonso, Agustín
A1 Harris, Claire L.
A1 de Cordoba, Santiago R.
A1 Morgan, Bryan P.
AB Atypical hemolytic uremic syndrome (aHUS) is associated with complement alternative pathway defects in over half the cases. Point mutations that affect complement surface regulation are common in factor H (CFH); however, sometimes individuals have null mutations in heterozygosis. The latter are difficult to identify, although a consistently low plasma factor H (fH) concentration is suggestive; definitive proof requires demonstration that the mutant sequence is not expressed in vitro. Here, novel reagents and assays that distinguish and individually quantify the common factor H-Y402H polymorphic variants were used to identify alleles of the CFH gene, resulting in low or null expression of full-length fH and also normal or increased expression of the alternative splice product factor H-like-1 (FHL-1). Our assay identified three Y402H heterozygotes with low or absent fH-H402 but normal or increased FHL-1-H402 levels in a cohort of affected patients. Novel mutations explained the null phenotype in two cases, which was confirmed by family studies in one. In the third case, family studies showed that a known mutation was present on the Y allele. The cause of reduced expression of the H allele was not found, although the data suggested altered splicing. In each family, inheritance of low expression or null alleles for fH strongly associated with aHUS. Thus, our assays provide a rapid means to identify fH expression defects without resorting to gene sequencing or expression analysis.
PB Elsevier
YR 2010
FD 2010-10-01
LK https://hdl.handle.net/20.500.14352/114423
UL https://hdl.handle.net/20.500.14352/114423
LA eng
NO Hakobyan S, Tortajada A, Harris CL, de Córdoba SR, Morgan BP. Variant-specific quantification of factor H in plasma identifies null alleles associated with atypical hemolytic uremic syndrome. Kidney Int. 2010 Oct;78(8):782-8. doi: 10.1038/ki.2010.275. Epub 2010 Aug 11. PMID: 20703214; PMCID: PMC3252682.
DS Docta Complutense
RD 29 abr 2025