Genetic deficiency of complement factor H in a patient with age-related macular degeneration and membranoproliferative glomerulonephritis
Genetic deficiency of complement factor H in a patient with age-related macular degeneration and membranoproliferative glomerulonephritis
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DOI：
10.1016/j.molimm.2008.01.027
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发表时间：
2008-05-01
影响因子：
3.6
通讯作者：
Rodriguez de Cordoba, Santiago
中科院分区：
文献类型：
--
作者：
Montes, Tamara;Goicoechea de Jorge, Elena;Rodriguez de Cordoba, Santiago
视网膜相关性黄斑变性（AMD）和II型膜增生性肾小球肾炎（MPGN 2）是与补体基因共享遗传关联的致密存款疾病，并且具有作为致密沉积物的重要组分的补体蛋白。在这里，我们介绍了一个64岁的吸烟男性谁开发的AMD和MPGN 2在他50多岁的情况下。该患者的血浆C3水平持续较低，H因子水平处于正常范围的较低部分，C3 NeF痕量。对CFH、CFB、C3、CFHR 1-CFHR 3和LOC 387715/HTRA 1基因的遗传分析显示，该患者是CFH外显子9中一种新的错义突变的杂合子（c. 1292 G > A），其导致因子H蛋白的SCR 7中的Cys 431 Tyr取代。此外，他是His 402 CFH等位基因的纯合子、Ser 69 LOC 387715等位基因的杂合子、Arg 32（BFS）CFB等位基因的纯合子、Gly 102（C3 F）C3等位基因的杂合子，并且没有携带CFHR 1/CFHR 3基因的缺失。蛋白质组学和功能分析表明血浆中不存在携带Cys 431 Tyr突变的因子H等位基因。总的来说，这些数据概括了原型补体遗传谱，包括部分因子H缺乏和AMD和MPGN 2的主要风险因子的存在，其支持这些致密存款疾病具有涉及补体激活的旁路途径失调的共同致病机制的假设。(c)2008爱思唯尔有限公司保留所有权利。
Age-related macular degeneration (AMD) and membranoproliferative glomerulonephritis type II (MPGN2) are dense deposit diseases that share a genetic association with complement genes and have complement proteins as important components of the dense deposits. Here, we present the case of a 64-year-old smoker male who developed both AMD and MPGN2 in his late 50s. The patient presented persistent low plasma levels of C3, factor H levels in the lower part of the normal range and C3NeF traces. Genetic analyses of the CFH, CFB, C3, CFHR1-CFHR3 and LOC387715/HTRA1 genes revealed that the patient was heterozygote for a novel missense mutation in exon 9 of CFH (c. 1292 G > A) that results in a Cys431Tyr substitution in SCR7 of the factor H protein. In addition, he was homozygote for the His402 CFH allele, heterozygote for the Ser69 LOC387715 allele, homozygote for the Arg32 (BFS) CFB allele, heterozygote for the Gly102 (C3F) C3 allele and carried no deletion of the CFHR1/CFHR3 genes. Proteomic and functional analyses indicate absence in plasma of the factor H allele carrying the Cys431Tyr mutation. As a whole, these data recapitulate a prototypical complement genetic profile, including a partial factor H deficiency and the presence of major risk factors for AMD and MPGN2, which support the hypothesis that these dense deposit diseases have a common pathogenic mechanism involving dysregulation of the alternative pathway of complement activation. (c) 2008 Elsevier Ltd. All rights reserved.