A novel hybrid CFHR1/CFH gene causes atypical hemolytic uremic syndrome.
A novel hybrid CFHR1/CFH gene causes atypical hemolytic uremic syndrome.
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DOI：
10.1007/s00467-013-2560-2
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发表时间：
2013-11
影响因子：
3
通讯作者：
Smith, Richard J. H.
中科院分区：
文献类型：
--
作者：
Eyler, Stephen J.;Meyer, Nicole C.;Zhang, Yuzhou;Xiao, Xue;Nester, Carla M.;Smith, Richard J. H.
关键词：
补体因子H(CFH)的突变与补体调节失调和侵袭性非典型溶血性尿毒症综合征(AHUS)的发展有关，aHUS发展为终末期肾病，在大多数患者移植后复发率很高。对CFH及其下游补体因子H相关基因(CFHR1-5)的序列分析表明，大量基因组重复导致了几个大的同源区块。这种高度的序列同源性使该区域易受非等位基因同源重组(Nahr)事件的影响，导致大规模的缺失、重复和杂交CFH基因的产生。在这里，我们报告了一个新的CFHR1/CFH杂合基因的发现，由从头开始的Nahr事件在一名患有AHUS的14岁女孩中产生。得到的融合蛋白包含CFHR1的前三个短共识重复序列(SCR)和CFH的末端两个SCR。这一发现表明了aHUS发生的一种新的致病机制。此外，由于标准的Sanger测序无法检测到这种重排，所有aHUS患者都应该接受全面的基因筛查，包括分析拷贝数变异，以确定临床预后较差的患者。
Mutations in complement factor H (CFH) are associated with complement dysregulation and the development of an aggressive form of atypical hemolytic uremic syndrome (aHUS) that progresses to end-stage renal disease and in most patients has a high rate of recurrence following transplantation. Sequence analysis of CFH and its downstream complement factor H-related genes (CFHR1-5) reveals several macrohomologous blocks caused by large genomic duplications. This high degree of sequence identity renders this area susceptible to nonallelic homologous recombination (NAHR) events, resulting in large-scale deletions, duplications, and the generation of hybrid CFH genes. Here, we report the finding of a novel CFHR1/CFH hybrid gene created by a de novo NAHR event in a 14-year-old girl with aHUS. The resulting fusion protein contains the first three short consensus repeats (SCRs) of CFHR1 and the terminal two SCRs of CFH. This finding demonstrates a novel pathogenic mechanism for the development of aHUS. Additionally, since standard Sanger sequencing is unable to detect such rearrangements, all aHUS patients should receive comprehensive genetic screening that includes analysis of copy number variation in order to identify patients with poor clinical prognoses.
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DOI：
10.2215/cjn.10181110
发表时间：
2011-06-01
影响因子：
9.8
作者：
Nester, Carla;Stewart, Zoe;Brophy, Patrick
通讯作者：
Brophy, Patrick
影响因子：
3.7
作者：
Loirat C;Frémeaux-Bacchi V
通讯作者：
Frémeaux-Bacchi V
DOI：
10.1053/j.ajkd.2010.06.021
发表时间：
2010-11
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Sethi S;Sukov WR;Zhang Y;Fervenza FC;Lager DJ;Miller DV;Cornell LD;Krishnan SG;Smith RJ
通讯作者：
Smith RJ
影响因子：
8.8
作者：
Krid, S.;Roumenina, L. T.;Niaudet, P.
通讯作者：
Niaudet, P.
影响因子：
13.6
作者：
Sellier-Leclerc, Anne-Laure;Fremeaux-Bacchi, Veronique;Loirat, Chantal
通讯作者：
Loirat, Chantal