A novel TRPC6 mutation in a family with podocytopathy and clinical variability

Abstract

Background: Mutation in several podocyte-specific genes have been noted to result in phenotypic heterogeneity. Herein, we report a novel, autosomal dominant TRPC6 mutation in a family with disease ranging from asymptomatic minimal change disease to end-stage kidney disease.

Case presentation: A 35 year old woman developed asymptomatic, nephrotic range proteinuria during pregnancy that did not resolve after delivery. Her mother had end-stage kidney disease of unknown etiology and her brother had asymptomatic proteinuria. Kidney biopsy revealed minimal change disease in both the proband and her brother. Genetic testing was performed in the proband and mother, revealing a novel frameshift mutation in TRPC6, D873fsX878. The proband continues to have subnephrotic range proteinuria and normal creatinine but her brother has since developed progressive chronic kidney disease.

Conclusions: The current case report underscores the heterogeneity of disease in podocytopathies and related genes. Genetic testing of podocyte genes is useful in order to understand the pathophysiologic processes underlying these overlapping diseases.

Figure 1

Genealogical tree of a non-consanguineous, Korean family with minimal change disease and a novel TRPC6 deletion mutation in exon 12.

Figure 2

Sequence analysis of the novel TRPC6 mutation found in 3 family members. Shown is a partial electropherogram of Sanger DNA sequencing analysis of TRPC6 exon12 from the proband. The arrow shows the position of the heterozygous four base pair deletion resulting in a downstream frameshift. Shown above are the nucleotide and predicted amino acid sequences of the wild-type TRPC6 sequence (top line) and the heterozygous four base pair deletion (bottom line). The deleted nucleotides (GATA) are depicted in red font. The four base pair deletion results in a frame shift and premature protein truncation, five amino acids downstream [p.D873fsX878].