TRPC6基因突变患者基因变异特征与临床病理及预后分析  

Genotypic and clinical features in patients with TRPC 6 gene mutations

作　　者：钟清 张昌明 朱丽 王钢 张丽华 刘志红 ZHONG Qing;ZHANG Changming;ZHU Li;WANG Gang;ZHANG Lihua;LIU Zhihong(National Clinical Research Center for Kidney Diseases,Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing 210016,China)

机构地区：[1]南京大学医学院附属金陵医院(东部战区总医院)国家肾脏疾病临床医学研究中心,南京210016

出　　处：《肾脏病与透析肾移植杂志》2024年第6期501-507,共7页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：国家自然科学基金面上项目(82170739)。

摘　　要：目的:探讨TRPC6基因突变患者的基因变异特征和临床病理表现。方法:筛选国家肾脏疾病临床医学研究中心经全外显子或肾脏疾病panel基因检测证实存在TRPC6基因突变患者,对患者的基因变异特征、临床病理及预后进行分析。结果:发现10例患者存在致病性TRPC6基因变异,共检测到TRPC6基因的8个杂合突变,其中6个为错义突变,以c.2683C>T(p.R895C)最为常见。肾脏病家族史阳性者9例。10例患者中,男女各5例,首次就诊年龄16~35岁。患者均以蛋白尿起病,4例起病即表现为肾病综合征(NS)。所有患者均接受过血管紧张素Ⅱ受体拮抗剂(ARB)治疗,5例患者接受足量激素联合钙调神经蛋白抑制剂(CNI)治疗,2例患者接受中等量激素治疗。6例患者于病程1~17年进展至终末期肾病(ESKD)。6例患者行肾活检病理表现均为局灶节段性肾小球硬化(FSGS),肾小球系膜增生不明显,部分患者伴轻至中度的慢性肾小管间质病变,超微结构下足细胞病变突出,足突广泛融合(50%~80%)4例、节段融合(30%~50%)2例,无肾小球基膜病变。结论:TRPC6基因变异以错义突变为主,最常见突变位点为c.2683C>T(p.R895C)。患者均以蛋白尿起病,半数为NS状态,肾脏病理以FSGS为主,足细胞足突融合明显,ARB及CNI治疗效果不佳,多数患者最终进展至ESKD。疾病的早期诊断和及时特异性干预治疗可能是改善预后的关键。Objective:To investigate the gene mutation characteristics and clinicopathological manifestations of patients with TRPC 6 gene mutation.Methodology:We screened our patients with TRPC 6 gene mutation confirmed by whole exon or nephropathy panel gene detection in the National Clinical Research Center for kidney Disease,and then analyzed the gene mutation characteristics,clinicopathology and prognosis of the patients.Results:A total of 10 patients were included in the study,of which 50%were male and 50%were female.8 heterozygous mutations of TRPC 6 gene were detected in the 10 patients,of which 6 were missense mutations,and c.2683C>T(p.R895C)was the most common.There were 9 cases with positive family history of kidney disease.The onset age of the patients was 16-35 years old,and all of them were onset with proteinuria,even 4 cases showed nephrotic syndrome(NS).All patients were treated with angiotensin II receptor blockers(ARB),of which 5 patients were treated with hormone combined with calcineurin inhibitors(CNI),and 2 patients were treated with moderate hormone.6 patients progressed to end-stage kidney disease(ESKD)in the course of 1-17 years.The pathological manifestations of renal biopsy in 6 patients were focal segmental glomerulosclerosis(FSGS),with 4 cases of foot process extensive fusion(50%-80%)and 2 cases of segmental fusion(30%-50%),and no glomerular basement membrane lesions.Conclusion:The mutation of TRPC 6 gene is mainly missense mutation,and the most common mutation site is c.2683C>T(p.R895C).The clinical manifestations of patients with related nephropathy are mainly proteinuria,most of which are NS.Renal pathology was mainly FSGS,and podocyte foot process fusion was obvious.Most patients have poor efficacy on ARB and CNIs,and eventually progress to ESKD.The early diagnosis and timely specific intervention of the disease may be the key to improve the prognosis of patients.

关 键 词：TRPC6基因变异 蛋白尿 局灶节段性肾小球硬化 终末期肾病 

分 类 号：R692[医药卫生—泌尿科学]