A Case of C3 Nephritis With a Rare Variant of the CFHR5 Gene

TL;DR

A young woman with C3 nephritis had a rare CFHR5 gene variant that may be linked to a better kidney outcome.

Contribution

A rare CFHR5 variant, P453S, is reported in a C3 nephritis case and suggested to influence disease progression and prognosis.

Findings

A heterozygous P453S variant in CFHR5 was identified in a patient with C3 nephritis.

The P453S variant is located in a functionally critical region of CFHR5 and is predicted to be pathogenic.

The patient's stable renal function suggests a possible favorable prognosis linked to this variant.

Abstract

C3 nephropathy is a renal disease caused by the aberrant activation of the alternative complement pathway. The long-term renal prognosis of C3 nephropathy is generally poor, and elucidation of its pathogenesis is clinically important. Genetic abnormalities within complement genes, encompassing autoantibodies targeting complement components and complement factor H-related proteins (CFHRs), can lead to abnormal complement activation. CFHR5 is one of the best-known responsible genes for C3 nephritis. Moreover, the renal prognosis can vary depending on the specific type of genetic mutation. Here, we report the case of a young woman with C3 nephritis and a heterozygous rare variant, P453S, in CFHR5. The P453S variant, characterized by amino acid substitutions with a low allele frequency, was located in the region essential for CFHR5 protein function, and multiple in silico analyses were done suggesting the pathological significance of P453S. The renal function of our patient remains stable. The P453S variant might contribute to the suppression of the CFHR5 protein’s function, resulting in gradual complement progression and a favorable renal prognosis.

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