{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T10:15:47Z","timestamp":1777025747983,"version":"3.51.4"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Mutations in the complement factor H (<jats:italic>CFH<\/jats: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 <jats:italic>CFH<\/jats:italic> and complement factor H-related (<jats:italic>CFHR<\/jats:italic>) gene regions have been identified in aHUS. However, one allele has both <jats:italic>CFHR<\/jats:italic> gene duplication and <jats:italic>CFH::CFHR1<\/jats: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\u2019s parents have no history of TMA. A genetic analysis revealed the presence of <jats:italic>CFH::CFHR1<\/jats:italic> fusion gene and a <jats:italic>CFHR3-1-4-2<\/jats:italic> gene duplication in the patient, her father, and her paternal grandfather. Although several fusion genes resulting from structural variations of the <jats:italic>CFH\u2013CFHR<\/jats:italic> genes region have been identified, this is the first report of the combination of a <jats:italic>CFH::CFHR1<\/jats:italic> fusion gene with <jats:italic>CFHR<\/jats:italic> gene duplication. Because the <jats:italic>CFH\u2013CFHR<\/jats:italic> region is highly homologous, we hypothesized that <jats:italic>CFHR<\/jats:italic> gene duplication occurred. These findings indicate a novel pathogenic genomic structural variation associated with the development of aHUS.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1360855","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T04:27:12Z","timestamp":1709872032000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case report: A family of atypical hemolytic uremic syndrome involving a CFH::CFHR1 fusion gene and CFHR3-1-4-2 gene 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