非典型溶血尿毒综合征
血栓性微血管病
CD46型
伊库利珠单抗
生物
系数H
基因
拷贝数变化
遗传学
补体系统
免疫学
人口
溶血
补体因子I
抗体
疾病
基因组
医学
内科学
环境卫生
作者
Yuka Sugawara,Hideki Kato,Masao Nagasaki,Yoko Yoshida,Madoka Fujisawa,Naoko Minegishi,Masayuki Yamamoto,Masaomi Nangaku
标识
DOI:10.1038/s10038-023-01129-1
摘要
Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated disease that manifests as the triad of thrombotic microangiopathy. We identified two aHUS patients with neither anti-complement factor H (CFH) antibodies nor causative variants of seven aHUS-related genes (CFH, CFI, CFB, C3, MCP, THBD, and DGKE); however, their plasma showed increased levels of hemolysis by hemolytic assay, which strongly suggests CFH-related abnormalities. Using a copy number variation (CNV) analysis of the CFH/CFHR gene cluster, we identified CFH-CFHR1 hybrid genes in these patients. We verified the absence of aHUS-related abnormal CNVs of the CFH gene in control genomes of 2036 individuals in the general population, which suggests that pathogenicity is related to these hybrid genes. Our study emphasizes that, for patients suspected of having aHUS, it is important to perform an integrated analysis based on a clinical examination, functional analysis, and detailed genetic investigation.
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