AUTHOR=Tasaki Yuko , Tsujimoto Hiroshi , Yokoyama Tadafumi , Sugimoto Naotoshi , Kitajima Shinji , Fujii Hiroshi , Hidaka Yoshihiko , Kato Noritoshi , Maruyama Shoichi , Inoue Norimitsu , Wada Taizo 

TITLE=Case report: A family of atypical hemolytic uremic syndrome involving a CFH::CFHR1 fusion gene and CFHR3-1-4-2 gene duplication

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1360855

DOI=10.3389/fimmu.2024.1360855

ISSN=1664-3224

ABSTRACT=<p>Mutations in the complement factor H (<italic>CFH</italic>) gene are associated with complement dysregulation and the development of atypical hemolytic uremic syndrome (aHUS). Several fusion genes that result from genomic structural variation in the <italic>CFH</italic> and complement factor H-related (<italic>CFHR</italic>) gene regions have been identified in aHUS. However, one allele has both <italic>CFHR</italic> gene duplication and <italic>CFH::CFHR1</italic> fusion gene have not been reported. An 8-month-old girl (proband) presented with aHUS and was treated with ravulizumab. Her paternal grandfather developed aHUS previously and her paternal great grandmother presented with anti-neutrophil cytoplasmic antibody-associated vasculitis and thrombotic microangiopathy (TMA). However, the proband’s parents have no history of TMA. A genetic analysis revealed the presence of <italic>CFH::CFHR1</italic> fusion gene and a <italic>CFHR3-1-4-2</italic> gene duplication in the patient, her father, and her paternal grandfather. Although several fusion genes resulting from structural variations of the <italic>CFH–CFHR</italic> genes region have been identified, this is the first report of the combination of a <italic>CFH::CFHR1</italic> fusion gene with <italic>CFHR</italic> gene duplication. Because the <italic>CFH–CFHR</italic> region is highly homologous, we hypothesized that <italic>CFHR</italic> gene duplication occurred. These findings indicate a novel pathogenic genomic structural variation associated with the development of aHUS.</p>