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Case Reports
. 2021 Jul;185(7):2175-2179.
doi: 10.1002/ajmg.a.62216. Epub 2021 Apr 21.

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

Hiroaki Hanafusa  1   2   3   4 , Yoshihiko Hidaka  5   6 , Tomomi Yamaguchi  1   2   3 , Hisashi Shimojo  7   8 , Takanori Tsukahara  9 , Tsubasa Murase  5 , Daisuke Matsuoka  5 , Nao Chiba  5 , Shun Shimada  5 , Hirokazu Morokawa  5 , Norio Omori  10 , Hironori Minoura  10 , China Nagano  11 , Kyoko Takano  1   2 , Katsuya Nakamura  1   2 , Keiko Wakui  1   2 , Yoshimitsu Fukushima  1   2 , Takeshi Uehara  7 , Yozo Nakazawa  5 , Kazumoto Iijima  11 , Kandai Nozu  11 , Tomoki Kosho  1   2   3   12
Affiliations
Case Reports

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

Hiroaki Hanafusa et al. Am J Med Genet A. 2021 Jul.

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.

Keywords: TRPC6; diffuse mesangial sclerosis; end-stage renal disease; infantile nephrotic syndrome; steroid-resistant nephrotic syndrome.

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References

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