A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 (<i>RCAN1</i>) Gene Confers Enhanced Calcineurin Activity and May Cause FSGS.

ABSTRACT:

Background

Podocyte dysfunction is the main pathologic mechanism driving the development of FSGS and other morphologic types of steroid-resistant nephrotic syndrome (SRNS). Despite significant progress, the genetic causes of most cases of SRNS have yet to be identified.

Methods

Whole-genome sequencing was performed on 320 individuals from 201 families with familial and sporadic NS/FSGS with no pathogenic mutations in any known NS/FSGS genes.

Results

Two variants in the gene encoding regulator of calcineurin type 1 (RCAN1) segregate with disease in two families with autosomal dominant FSGS/SRNS. In vitro, loss of RCAN1 reduced human podocyte viability due to increased calcineurin activity. Cells expressing mutant RCAN1 displayed increased ca

SUBMITTER: Lane BM 

PROVIDER: S-EPMC8425665 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature