TY - JOUR
T1 - CFH-CFHR1 hybrid genes in two cases of atypical hemolytic uremic syndrome
AU - Sugawara, Yuka
AU - Kato, Hideki
AU - Nagasaki, Masao
AU - Yoshida, Yoko
AU - Fujisawa, Madoka
AU - Minegishi, Naoko
AU - Yamamoto, Masayuki
AU - Nangaku, Masaomi
N1 - Funding Information:
This study was supported by research grants from the Japanese Association for Complement Research, and the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development, AMED (17ek0109254h0001). This work was partially supported by “Joint Usage/Research Center for Interdisciplinary Large-scale Information Infrastructures” and “High Performance Computing Infrastructure” in Japan (Project IDs: jh210018-NWH and jh220014). Open access funding provided by The University of Tokyo.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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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U2 - 10.1038/s10038-023-01129-1
DO - 10.1038/s10038-023-01129-1
M3 - Article
AN - SCOPUS:85147670950
SN - 1434-5161
JO - Jinrui idengaku zasshi. The Japanese journal of human genetics
JF - Jinrui idengaku zasshi. The Japanese journal of human genetics
ER -