Analysis of variants in complement genes in Han Chinese children with atypical hemolytic uremic syndrome / 中华儿科杂志

ABSTRACT

Objective@#To investigate the prevalence and characteristics of pathogenic variants in complement genes in Han Chinese children with atypical hemolytic uremic syndrome (aHUS).@*Method@#Eleven Han Chinese children with aHUS, including 9 boys and 2 girls aged between 1 year and 4 months and 13 years, were investigated in Department of Pediatrics, Fuzhou General Hospital, from November 1998 to February 2014. Analysis of variants of all the exons of 10 complement genes (CFH, MCP, CFI, C3, CFB, CFHR1, CFHR2, CFHR3, CFHR4 and CFHR5), including 25 bases from 3′ end and 25 bases from 5' end, was performed in the 11 cases by targeted sequence capture and next generation sequencing. Significant variants detected by next generation sequencing were confirmed by Sanger sequencing. To understand pathogenicity of variants found in the captured genes, we investigated genetic conservation by multiple protein sequence alignment among different species, and analyzed whether the variants were located in protein domains or not, and investigated functional significance by functional computational prediction methods.@*Result@#Twenty-seven percent of Han Chinese children with aHUS carried pathogenic variants in the 10 complement genes. Pathogenic variant CFB 221G>A (R74H) was detected in Patient 3 and Patient 9, which was not found in parents of Patient 3′ , and was found in healthy father of patient 9. Pathogenic variant CFHR5 242C>T (P81L) was found in Patient 2, and was found in healthy father of patient 2. However, no pathogenic variants in genes CFH, MCP, CFI, C3, CFHR1, CFHR2, CFHR3 and CFHR4 were identified.@*Conclusion@#Pathogenic variants in the 10 complement genes were identified in 3/11 of Han Chinese children with aHUS in our study and CFB was the most frequently mutated gene.