# Compound heterozygous variants of ANKFY1 in a child with infantile-onset proteinuria and movement disorder

## TL;DR

A child with kidney and movement issues was found to have rare genetic changes in the ANKFY1 gene, suggesting a new syndrome.

## Contribution

This is the first report of a neuro-renal syndrome associated with bi-allelic ANKFY1 variants.

## Key findings

- Compound heterozygous variants in ANKFY1 were identified in a child with infantile-onset proteinuria and movement disorder.
- The variants reduced ANKFY1 protein expression in vitro.
- This case suggests a new neuro-renal syndrome linked to ANKFY1 mutations.

## Abstract

The ANKFY1 gene encodes a protein that belongs to double zinc finger proteins involved in endocytosis. Only one family with steroid-resistant nephrotic syndrome has been reported carrying a homozygous variant in ANKFY1 so far. Here we describe the second case where a 13-year-old boy presented with infantile-onset proteinuria and movement disorder. Whole-exome sequencing showed compound heterozygous variants (NM_001330063.2: c.2753C>G; p.Ser918Ter, and c.3287–11_3287–10del) in ANKFY1. In vitro functional study revealed the two variants led to reduced protein expression level of ANKFY1. This is the first case of co-existence of renal and nervous system phenotypes in a child with variants in ANKFY1, suggesting that bi-allelic variants in ANKFY1 might be associated with a new neuro-renal syndrome.