CFH-CFHR1 Hybrid Genes in Two Cases of Atypical Hemolytic Uremic Syndrome

Overview

Journal J Hum Genet

Specialty Genetics

Date 2023 Feb 9

PMID 36755127

Authors

Yuka Sugawara

Hideki Kato

Masao Nagasaki

Yoko Yoshida

Madoka Fujisawa

Naoko Minegishi

Masayuki Yamamoto

Masaomi Nangaku

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation?.

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