Heterozygous missense variant in TRPC6 in a boy with rapidly progressive infantile nephrotic syndrome associated with diffuse mesangial sclerosis

Abstract

Transient receptor potential channel C6 encoded by TRPC6 is involved in slit diaphragm formation in podocytes, and abnormalities of the TRPC6 protein cause various glomerular diseases. The first identified pathogenic variant of TRPC6 was found to cause steroid‐resistant nephrotic syndrome that typically developed in adulthood and then slowly led to end‐stage renal disease, along with a renal pathology of focal segmental glomerulosclerosis. Here, we report a patient with rapidly progressing infantile nephrotic syndrome and a heterozygous missense TRPC6 variant. The patient, a 2‐year‐old Japanese boy, developed steroid‐resistant nephrotic syndrome at age 11 months. His renal function deteriorated rapidly, and peritoneal dialysis was introduced at age 1 year and 6 months. His renal pathology, obtained at age 1 year and 1 month, was consistent with diffuse mesangial sclerosis (DMS). Clinical exome analysis and custom panel analysis for hereditary renal diseases revealed a reported heterozygous missense variant in TRPC6 (NM_004621.5:c.523C > T:p.Arg175Trp). This is the first report of a patient with a TRPC6‐related renal disorder associated with DMS.

Mutation analysis of TRPC6 gene in nephrotic syndrome in children from a single center

“…Mutations in the TRPC6 gene play an important role in primary nephrotic syndrome in human children.Weizhen Tan et al [18] American scholars used microfluidic technique of high-throughput PCR to analyze mutations in 24 single genes in children with SRNS from 72 families, and as a result, mutations in the TRPC6 gene were detected (c.2683C>T, p.R895C, heterozygous), which confirms that the TRPC6 gene can cause FSGS. In addition, according to the report, Japanese researchers found for the first time that a boy aged one year and one month suffered from diffuse mesenchymal sclerosis (DMS) due to a heterozygous missense mutation in the TRPC6 gene (NM_004621.5: c.523C > T: p.Arg175Trp) [19], which suggests that the TRPC6 Joshi B B, Koringa PG et al [8] Indian scholars conformationally analyzed and verified that both mutations in TRPC6 (N157T, rs35857503; A404V, rs36111323) are important influences in causing FSGS in almost all four instruments. Wang F,ZhangY et al [20] Chinese scholars performed gene sequencing on 110 children with SRNS from five research centers in China and detected a de novo missense mutation in TRPC6 (c.523C＞T, p.Arg175Trp) in one case of infantile nephrotic syndrome, suggesting that mutations in the TRPC6 gene would lead to infantile nephrotic syndrome This suggests that TRPC6 mutations will lead to the development of nephrotic syndrome in infants and children.…”

Novel NUP93 Gene Variant and Diffuse Mesangial Sclerosis in Steroid Resistant Nephrotic Syndrome

“…Diffuse mesangial sclerosis is a well-known biopsy finding in patients of syndromic SRNS with genetic mutation in WT1 gene, LAMB2 [1], PLCE1 [2], TRPC6 [3] etc. One patient in a case series of NUP93 gene mutation with SRNS was noted to have DMS/focal segmental glomerulosclerosis (FSGS) [4].…”