Screening of ACTN4 and TRPC6 Mutations in a Chinese Cohort of Patients with Adult-Onset Familial Focal Segmental Glomerulosclerosis
Screening of ACTN4 and TRPC6 Mutations in a Chinese Cohort of Patients with Adult-Onset Familial Focal Segmental Glomerulosclerosis
复制标题
中国成年发病家族性局灶节段性肾小球硬化症患者队列中 ACTN4 和 TRPC6 突变的筛查。
DOI：
10.1159/000348471
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发表时间：
2013-01-01
期刊：
影响因子：
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通讯作者：
Chen, Nan
中科院分区：
文献类型：
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作者：
Zhang, Qianying;Ma, Jun;Chen, Nan
目的：家族性局灶节段性肾小球硬化（FSGS）已被广泛报道为其发病机制具有潜在的遗传成分。近年来，TRPC6和ACTN4基因突变被发现与家族性FSGS相关，但这两个基因在中国家族性FSGS患者中的突变率研究较少。本研究的目的是确定中国成人发病家族性FSGS中TRPC6和ACTN4突变的患病率。方法：对我院1997年9月至2012年1月收治的80例中国血统FSGS家系进行TRPC6和ACTN4突变筛查。每个家庭至少有一个活检证实的FSGS。如果家庭中只有1例活检证实的FSGS病例，则需要另一名肾功能不全、明显蛋白尿或终末期肾病的家庭成员。继发于全身性疾病（如肥胖、高血压、糖尿病或病毒感染）的FSGS被排除在外。其他遗传性肾脏疾病，如阿尔波特病和法布里病，也被相关检测排除。从外周血中提取基因组DNA，对本研究所有FSGS家系先证中TRPC6和ACTN4的所有外显子和外显子-内含子边界进行Sanger测序。结果：总指数患者中，女性33例，男性47例。发病的中位年龄为39岁（15-67岁）。诊断时中位蛋白尿水平为1324 mg/天，中位血清肌酐水平为114.5 mu mol/l（范围41- 1040）。在两个独立的家族中发现TRPC6错义突变（Q889K）。未发现ACTN4突变。因此，TRPC6的突变率为2.5%，ACTN4的突变率为0%。结论：中国家族性FSGS患者中TRPC6和ACTN4突变仅占少数。在这些患者中进行进一步的遗传学研究将有助于增加我们对FSGS发病机制的理解。巴塞尔S. Karger股份有限公司版权所有
Objectives: Familial focal segmental glomerulosclerosis (FSGS) has been widely reported as having an underlining genetic component to its pathogenesis. Recently, mutations in TRPC6 and ACTN4 were identified to be associated with familial FSGS, however few studies have reported the mutation rates of these two genes in Chinese familial FSGS patients. The aim of this study was to determine the prevalence of TRPC6 and ACTN4 mutations in Chinese adult-onset familial FSGS. Methods: 80 FSGS pedigrees with Chinese ancestry who were admitted to our hospital from September 1997 to January 2012 were screened for TRPC6 and ACTN4 mutations. There was at least one biopsy-proven FSGS in each family. An additional family member with renal function insufficiency, obvious proteinuria, or end-stage renal disease was required if there was only 1 biopsy-proven FSGS case in the family. FSGS secondary to systemic diseases, such as obesity, hypertension, diabetes, or virus infection, were excluded. Other hereditary renal diseases, such as Alport's disease and Fabry disease, were also excluded by related tests. Genomic DNA was extracted from peripheral blood cells, and Sanger sequencing was performed for all exons and exon-intron boundaries of TRPC6 and ACTN4 in the probands of all FSGS pedigrees enrolled in this study. Results: Of the total index patients, 33 were female and 47 were male. The median age at disease onset was 39 years (range 15-67). The median proteinuria level was 1,324 mg/day and the median serum creatinine level was 114.5 mu mol/l (range 41-1,040) at diagnosis. A missense mutation (Q889K) of TRPC6 was found in two independent families. No mutation was found in ACTN4. Accordingly, the mutation rate of TRPC6 was 2.5% and of ACTN4 it was 0%. Conclusion: Mutations of TRPC6 and ACTN4 occur in only a minor portion of Chinese familial FSGS patients. Further genetic studies conducted in these patients will be helpful to increase our understanding of the pathogenesis of FSGS. Copyright (C) 2013 S. Karger AG, Basel