Sequence and copy number variations in the human CFHR-Factor H gene cluster comprising the complement genes CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, and Factor H are linked to the human kidney diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy. Distinct genetic and chromosomal alterations, deletions, or duplications generate hybrid or mutant CFHR genes, as well as hybrid CFHR-Factor H genes, and alter the FHR and Factor H plasma repertoire. A clear association between the genetic modifications and the pathologic outcome is emerging: CFHR1, CFHR3, and Factor H gene alterations combined with intact CFHR2, CFHR4, and CFHR5 genes are reported in atypical hemolytic uremic syndrome. But alterations in each of the five CFHR genes in the context of an intact Factor H gene are described in C3 glomerulopathy. These genetic modifications influence complement function and the interplay of the five FHR proteins with each other and with Factor H. Understanding how mutant or hybrid FHR proteins, Factor H::FHR hybrid proteins, and altered Factor H, FHR plasma profiles cause pathology is of high interest for diagnosis and therapy.

中文翻译：

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CFHR 基因变异为肾脏疾病非典型溶血性尿毒症综合征和 C3 肾小球病的发病机制提供了见解。

包含补体基因 CFHR1、CFHR2、CFHR3、CFHR4、CFHR5 和 H 因子的人类 CFHR-因子 H 基因簇中的序列和拷贝数变异与人类肾脏疾病非典型溶血性尿毒症综合征 (aHUS) 和 C3 肾小球病有关。独特的遗传和染色体改变、缺失或重复产生杂合或突变的CFHR基因，以及杂合的CFHR-H因子基因，并改变FHR和H因子血浆库。基因修饰与病理结果之间的明显关联正在显现：在非典型溶血性尿毒症综合征中，CFHR1、CFHR3 和 H 因子基因改变与完整的 CFHR2、CFHR4 和 CFHR5 基因相结合。但在 C3 肾小球病中描述了在完整的 H 因子基因背景下五个 CFHR 基因中每一个的改变。这些基因修饰影响补体功能以及五种 FHR 蛋白彼此之间以及与 H 因子的相互作用。了解突变或杂合 FHR 蛋白、H 因子::FHR 杂合蛋白以及 H 因子、FHR 血浆谱的改变如何导致病理学具有重要意义。对诊断和治疗有浓厚的兴趣。