Whole-exome sequencing detects mutations in pediatric patients with atypical hemolytic uremic syndrome in Taiwan
Journal
Clinica Chimica Acta
Journal Volume
494
Pages
143-150
Date Issued
2019
Author(s)
Abstract
Although atypical hemolytic uremic syndrome (aHUS) is a genetic disorder, molecular defects are detected in only 60% of patients. We aim to dissect the genetic background by whole exome sequence and the clinical characteristics of pediatric patients with aHUS. Ten patients (6 male and 4 female) with mean age 5.2 ± 5.0 years were enrolled. The age at onset ranged from 2 days to 11 years. Eighteen different mutations (17 missense, 2 nonsense, and 11 novel) on 7 complement and 3 coagulation genes were detected in all patients. The majority of mutation was heterozygous and S1191L on CFH were the recurrent mutation. Sixty percent of patients had multiple genetic mutations. Nine mutations were associated with genes known to be implicated in aHUS (CFH, CFI, CD46, CFHR5, and DGKE), while 4 and 5 mutations were detected on complement- (C8B, C9, and MASP1) and coagulation-associated (VWF and CD36) genes, respectively. CD36 may be a candidate gene act as disease modifier for aHUS through the contribution of thrombosis by impairing the interaction with TSP-1 and ADAMTS 13 shown in simulation model. Genetic defects on both complement and coagulation pathways play pathogenic roles on aHUS. CD36 may be a novel candidate gene act as disease modifier of aHUS. ? 2019 Elsevier B.V.
Subjects
Atypical hemolytic uremic syndrome; Coagulation; Complement regulatory protein; Thrombotic microangiopathy; Whole exome sequence
SDGs
Other Subjects
CD36 antigen; complement component C8b; complement component C9; complement factor H; complement factor I; diacylglycerol kinase; mannan binding lectin associated serine proteinase; membrane cofactor protein; thrombospondin 1; von Willebrand factor; von Willebrand factor cleaving proteinase; CD36 antigen; adolescent; Article; blood clotting; C8B gene; C9 gene; CD36 gene; CD46 gene; CFH gene; CFHR5 gene; CFI gene; child; clinical article; complement system; DGKE gene; female; gene mutation; genetic disorder; hemolytic uremic syndrome; heterozygosity; human; infant; male; MASP1 gene; missense mutation; newborn; nonsense mutation; onset age; pathogenesis; priority journal; protein interaction; simulation; Taiwan; thrombosis; VWF gene; whole exome sequencing; genetics; hemolytic uremic syndrome; mutation; preschool child; Adolescent; Atypical Hemolytic Uremic Syndrome; CD36 Antigens; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Mutation; Taiwan; Whole Exome Sequencing
Publisher
Elsevier B.V.
Type
journal article