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

• Published in: American journal of medical genetics. Part A 2021-07, Vol.185 (7), p.2175-2179
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Age; Child, Preschool; diffuse mesangial sclerosis; end‐stage renal disease; Exome - genetics; Genetic Predisposition to Disease; Glomerulosclerosis, Focal Segmental - complications; Glomerulosclerosis, Focal Segmental - diagnostic imaging; Glomerulosclerosis, Focal Segmental - genetics; Glomerulosclerosis, Focal Segmental - pathology; Heterozygote; Humans; Infant; infantile nephrotic syndrome; Kidney - diagnostic imaging; Kidney - pathology; Kidney diseases; Kidney Diseases - complications; Kidney Diseases - diagnostic imaging; Kidney Diseases - genetics; Kidney Diseases - pathology; Male; Mutation, Missense - genetics; Nephrotic syndrome; Nephrotic Syndrome - complications; Nephrotic Syndrome - diagnostic imaging; Nephrotic Syndrome - genetics; Nephrotic Syndrome - pathology; Peritoneal dialysis; Peritoneum; Podocytes - metabolism; Podocytes - pathology; Renal function; Sclerosis; Sclerosis - complications; Sclerosis - diagnostic imaging; Sclerosis - genetics; Sclerosis - pathology; Steroids; steroid‐resistant nephrotic syndrome; Transient receptor potential proteins; TRPC6; TRPC6 Cation Channel - genetics
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.62216

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.