부산대학교 도서관

Complement factor H (CFH) and its related proteins have an essential role in regulating the alternative pathway of the complement system. Mutations and structural variants (SVs) of the CFHgene cluster, consisting of CFHand its five related genes (CFHR1-5), have been reported in renal pathologies as well as in complex immune diseases like age-related macular degeneration and systemic lupus erythematosus. SV analysis of this cluster is challenging due to its high degree of sequence homology. Following first-line NGS gene panel sequencing, we applied Genomic Vision’s Molecular Combing Technology, to detect and visualize SVs within the CFHgene cluster and resolve its structural haplotypes completely. This approach was tested in three patients with atypical hemolytic uremic syndrome (aHUS) and known SVs, and 18 patients with aHUS or complement factor 3 glomerulopathy with unknown CFHgene cluster haplotypes. Three SVs, a CFH/CFHR1hybrid gene in two patients and a rare heterozygous CFHR4/CFHR1deletion in transwith the common CFHR3/CFHR1deletion in a third patient were newly identified. For the latter, the breakpoints were determined using a targeted enrichment approach for long DNA fragments (Samplix Xdrop) in combination with Oxford Nanopore sequencing.