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

Abstract: Objective: To  investigate  the  gene  mutation  characteristics  and  clinicopathological  manifestations  of patients with TRPC6  gene  mutation.     Methodology: We  screened  our  patients  with  TRPC6  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 TRPC6 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 TRPC6 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.

Key words: TRPC6 gene mutation   , proteinuria   , focal segmental glomerulosclerosis   , end?stage kidney disease