Expansion of the genotypic and phenotypic spectrum and treatment of four children with Steroid-resistant nephrotic syndrome due to variants of TRPC6 gene
10.3760/cma.j.cn511374-20230309-00120
- VernacularTitle:TRPC6变异致激素耐药型肾病综合征4例患儿的基因型和表型谱扩展及治疗分析
- Author:
Gongping ZHAO
1
;
Jitong LI
;
Yujie LIU
;
Guangbo LI
;
Yanmin ZHANG
;
Shufeng ZHANG
;
Cuihua LIU
Author Information
1. 郑州大学附属儿童医院 河南省儿童医院 郑州儿童医院肾脏风湿科 郑州市儿童肾脏病研究重点实验室，郑州 450018
- Keywords:
TRPC6 gene;
Nephrotic syndrome;
Steroid resistance;
Children
- From:
Chinese Journal of Medical Genetics
2024;41(4):473-479
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical and genetic characteristics, treatment and prognosis of four children with Steroid-resistant nephrotic syndrome (SRNS) due to variants of TRPC6 gene. Methods:Clinical data of four children with SRNS admitted to Children′s Hospital Affiliated to Zhengzhou University between May 2020 and August 2022 were collected. Peripheral blood samples were collected from the children and their parents, and whole exome sequencing was carried out. Sanger sequencing was used to verify the pathogenicity of the candidate variants among the children and their parents.Results:All of the four children were found to harbor heterozygous variants of the TRPC6 gene, including c. 523C>T (p.R175W), c. 1327T>A (p.F443I), c. 430G>C (p.E144Q) (unreported previously), and c. 523C>T (p.R175W), which were all missense variants. Two of the children have shown a simple type, whilst two have shown a nephritis type, none had extrarenal phenotype. Comprehensive renal pathology of three children revealed focal segmental glomerulosclerosis (FSGS). Two children were treated with steroids combined with calcineurin inhibitors (CNIs), among whom one showed significant improvement in symptoms. Conclusion:Discoveries of the novel c. 430G>C variant and the new SRNS phenotype of the c. 1327T>A variant have expanded the mutational and phenotypic spectrum of the TRPC6 gene, which has provided a reference for clinical diagnosis and genetic counseling for the families.
