Premium
Heterozygous missense variant in TRPC6 in a boy with rapidly progressive infantile nephrotic syndrome associated with diffuse mesangial sclerosis
Author(s) -
Hanafusa Hiroaki,
Hidaka Yoshihiko,
Yamaguchi Tomomi,
Shimojo Hisashi,
Tsukahara Takanori,
Murase Tsubasa,
Matsuoka Daisuke,
Chiba Nao,
Shimada Shun,
Morokawa Hirokazu,
Omori Norio,
Minoura Hironori,
Nagano China,
Takano Kyoko,
Nakamura Katsuya,
Wakui Keiko,
Fukushima Yoshimitsu,
Uehara Takeshi,
Nakazawa Yozo,
Iijima Kazumoto,
Nozu Kandai,
Kosho Tomoki
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62216
Subject(s) - trpc6 , nephrotic syndrome , focal segmental glomerulosclerosis , missense mutation , medicine , glomerulosclerosis , slit diaphragm , renal function , endocrinology , pathology , glomerulonephritis , kidney , biology , podocyte , proteinuria , phenotype , genetics , receptor , transient receptor potential channel , gene
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.