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  

Expansion of the genotypic and phenotypic spectrum and treatment of four children with Steroid-resistant nephrotic syndrome due to variants of TRPC6 gene

作　　者：赵公平 李纪同 刘玉洁[1] 李广波 张艳敏[1] 张书锋[1] 刘翠华[1] Zhao Gongping;Li Jitong;Liu Yujie;Li Guangbo;Zhang Yanmin;Zhang Shufeng;Liu Cuihua(Department of Nephrology and Rheumatology,Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou Children′s Hospital,Zhengzhou Key Laboratory of Children′s Kidney Disease Research,Zhengzhou,Henan 450018,China;Henan Provincial Key Laboratory of Children′s Genetics and Metabolic Diseases,Zhengzhou,Henan 450018,China)

机构地区：[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 [2]河南省儿童遗传代谢性疾病重点实验室,郑州450018

出　　处：《中华医学遗传学杂志》2024年第4期473-479,共7页Chinese Journal of Medical Genetics

基　　金：河南省医学科技攻关计划省部共建重点项目(SBGJ202002124);河南省科技攻关计划(212102310441、192102310074)。

摘　　要：目的总结4例TRPC6基因变异致激素耐药型肾病综合征(SRNS)患儿的临床特征、遗传学特点、治疗及预后。方法收集2020年5月至2022年8月于郑州大学附属儿童医院肾脏风湿科住院的4例SRNS患儿的临床资料。提取4例患儿及其父母外周血DNA,对患儿进行全外显子组基因测序,应用Sanger测序对患儿及其父母进行变异位点验证及致病性分析。结果4例患儿携带的TRPC6基因变异分别为:c.523C>T(p.R175W)、c.1327T>A(p.F443I)、c.430G>C(p.E144Q)(国内外均未见报道)、c.523C>T(p.R175W),均为错义变异。4例SRNS患儿中,2例表现为单纯型,2例为肾炎型,均无肾外表型,其中3例患儿完善肾脏病理均为局灶节段性肾小球硬化(FSGS)。2例患儿进行了激素联合钙调磷酸酶抑制剂(CNIs)治疗,其中1例症状明显改善。结论TRPC6基因c.430G>C变异为新变异位点,c.1327T>A变异可能会导致SRNS新表型,扩展了该基因的变异谱和表型谱,为该病患儿临床诊断与遗传咨询提供参考依据。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.

关 键 词：TRPC6基因 肾病综合征 激素耐药 儿童 

分 类 号：R726.9[医药卫生—儿科]