Whole-exome sequencing detects mutations in pediatric patients with atypical hemolytic uremic syndrome in Taiwan.
Whole-exome sequencing detects mutations in pediatric patients with atypical hemolytic uremic syndrome in Taiwan.
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DOI：
10.1016/j.cca.2019.03.1623
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发表时间：
2019-07
期刊：
影响因子：
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通讯作者：
Min-Hua Tseng;J. Tsai;I. Tsai;Shih-Ming Huang;Jing-Long Huang;W. Fan;Hwei-Jen Lee;Tai-Wei Wu;Shih-Hua Lin
中科院分区：
文献类型：
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作者：
Min-Hua Tseng;J. Tsai;I. Tsai;Shih-Ming Huang;Jing-Long Huang;W. Fan;Hwei-Jen Lee;Tai-Wei Wu;Shih-Hua Lin
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 andCD36) genes, respectively.CD36may 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.CD36may be a novel candidate gene act as disease modifier of aHUS.
