Kamido Hisashi, Yamamoto Shinya, Yokoi Hideki, Mizuno Masashi, Yanagita Motoko
Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, JPN.
Nephrology, Nagoya University, Nagoya, JPN.
Cureus. 2024 Feb 27;16(2):e55102. doi: 10.7759/cureus.55102. eCollection 2024 Feb.
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. 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 . 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.
C3 肾病是一种由替代补体途径异常激活引起的肾脏疾病。C3 肾病的长期肾脏预后通常较差，阐明其发病机制具有重要的临床意义。补体基因内的遗传异常，包括针对补体成分的自身抗体和补体因子 H 相关蛋白（CFHRs），可导致补体异常激活。 是 C3 肾炎最著名的致病基因之一。此外，肾脏预后可能因基因突变的具体类型而异。在此，我们报告一例患有 C3 肾炎且在 中存在杂合罕见变异 P453S 的年轻女性病例。P453S 变异以低等位基因频率的氨基酸替换为特征，位于 CFHR5 蛋白功能所必需的区域，并且进行了多项计算机模拟分析，提示 P453S 的病理意义。我们患者的肾功能保持稳定。P453S 变异可能有助于抑制 CFHR5 蛋白的功能，导致补体逐渐进展以及良好的肾脏预后。
