Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis.
Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis.
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DOI：
10.1186/s40246-022-00430-y
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发表时间：
2022-11-12
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
局灶节段性肾小球硬化症（FSGS）是一种组织病理学表现，是多种疾病的特征。此前已对许多与FSGS相关的基因展开研究，但文献中仍有一些FSGS家系，未发现已知的基因突变。本研究旨在探究成人起病的FSGS新的遗传病因。
本研究纳入40个FSGS家系、77例散发FSGS病例、157个非FSGS慢性肾脏病（CKD）家系以及195名健康对照进行分析。对所有招募家系的先证者及家庭成员、散发FSGS病例进行全外显子测序（WES）和桑格测序。
通过WES，我们在两个分别患有FSGS和CKD的家系（FS - 133和CKD - 05）中，发现了输出蛋白5基因（XPO5）的一个新的杂合错义变异（c.T1655C:p.V552A）。桑格测序证实，该变异在这两个家系中以常染色体显性模式共分离，而在健康对照中不存在。此外，通过桑格测序发现，195名种族匹配的健康对照中均无此变异。随后，计算机模拟分析表明，所发现的变异在进化上高度保守，很可能具有致病性。
我们的研究首次报道了XPO5变异在家族性FSGS中呈成人起病的常染色体显性遗传。本研究拓展了对该基因突变的基因型、表型及种族谱的认识。
网络版包含补充材料，网址为10.1186/s40246 - 022 - 00430 - y。
Focal and segmental glomerulosclerosis (FSGS) is a histological pathology that characterizes a wide spectrum of diseases. Many genes associated with FSGS have been studied previously, but there are still some FSGS families reported in the literature without the identification of known gene mutations. The aim of this study was to investigate the new genetic cause of adult-onset FSGS. This study included 40 FSGS families, 77 sporadic FSGS cases, 157 non-FSGS chronic kidney disease (CKD) families and 195 healthy controls for analyses. Whole-exome sequencing (WES) and Sanger sequencing were performed on probands and family members of all recruited families and sporadic FSGS cases. Using WES, we have identified a novel heterozygous missense variant (c.T1655C:p.V552A) in exportin 5 gene (XPO5) in two families (FS-133 and CKD-05) affected with FSGS and CKD. Sanger sequencing has confirmed the co-segregation of this identified variant in an autosomal dominant pattern within two families, while this variant was absent in healthy controls. Furthermore, the identified mutation was absent in 195 ethnically matched healthy controls by Sanger sequencing. Subsequently, in silico analysis demonstrated that the identified variant was highly conservative in evolution and likely to be pathogenic. Our study reports an adult-onset autosomal dominant inheritance of the XPO5 variant in familial FSGS for the first time. Our study expanded the understanding of the genotypic, phenotypic and ethnical spectrum of mutation in this gene. The online version contains supplementary material available at 10.1186/s40246-022-00430-y.
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影响因子：
9.8
作者：
Gee, Heon Yung;Ashraf, Shazia;Hildebrandt, Friedhelm
通讯作者：
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影响因子：
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通讯作者：
Perlman EJ
影响因子：
5.3
作者：
Okada N;Ishigami Y;Suzuki T;Kaneko A;Yasui K;Fukutomi R;Isemura M
通讯作者：
Isemura M
影响因子：
9.8
作者：
Ebarasi, Lwaki;Ashraf, Shazia;Majumdar, Arindam
通讯作者：
Majumdar, Arindam
中国大陆原发性肾小球肾炎：概述
DOI：
10.1159/000348642
发表时间：
2013-01-01
期刊：
NEW INSIGHTS INTO GLOMERULONEPHRITIS: PATHOGENESIS AND TREATMENT
影响因子：
--
作者：
Xie, Jingyuan;Chen, Nan
通讯作者：
Chen, Nan