A case report of XXXX without @entity8 carrying two novel mutations in complement-regulator genes.

@entity9818 @entity1 @entity8 @entity60960 @entity71435 @entity2105 @entity71437 @entity71438 @entity16 @entity2881 @entity9820 @entity1381 @entity71436 @entity2106
BACKGROUND: @entity9818 ( @entity9818 ) often represent a challenge for clinicians, because clinical, laboratory and even genetic features are not always sufficient to distinguish among different @entity9818 . OBJECTIVES: The aim of this study was to investigate the pathogenetic mechanisms underlying an acute case of TMA with features of both @entity2106 and @entity1381 . @entity1 /METHODS: We report the case of a 49-year-old @entity1 who developed an acute TMA with neurologic involvement and no @entity8 . @entity2105 , @entity2881 and complement-system biochemical characterization was performed on acute phase samples. Exome sequencing and direct Sanger sequencing of previously aHUS-associated genes were performed. The functional consequences of the @entity9820 ( @entity9820 ) mutation were investigated by in vitro expression studies. RESULTS: Despite a clinical diagnosis of @entity2106 , the @entity1 had normal @entity2105 levels and increased @entity2881 antigen levels with ultra-large @entity2881 multimers. C3, @entity71435 (CFI) were normal. Molecular analysis confirmed two novel heterozygous mutations in CFI ( @entity71436 , @entity60960 ) and @entity9820 ( @entity71437 , @entity71438 ) and in vitro expression studies showed a reduction in the generation of TAFIa caused by mutated @entity9820 . This pro-inflammatory condition, associated with the @entity60960 mutation in CFI, probably leads to a complement-mediated endothelial activation, with a relevant prothrombotic potential in case of transient environmental triggers. CONCLUSIONS: This study identified the first case of acute TMA without @entity8 but with @entity16 carrying two novel mutations in complement-regulator genes, highlighting the possible role of the complement system as a common pathogenetic mechanism in @entity9818 . This article is protected by copyright. All rights reserved.
