Hemizygous loss of function mutations in CLCN5 causing end-stage kidney disease without Dent disease phenotype

Gary Leggatt; Christine Gast; Rodney D Gilbert; Kristin Veighey; Tahmina Rahman; Sarah Ennis

doi:10.1093/ckj/sfac127

Hemizygous loss of function mutations in CLCN5 causing end-stage kidney disease without Dent disease phenotype

Clin Kidney J. 2022 May 7;16(1):192-194. doi: 10.1093/ckj/sfac127. eCollection 2023 Jan.

Authors

Gary Leggatt^{1

2}, Christine Gast^{1

2}, Rodney D Gilbert^{1

3}, Kristin Veighey^{1

2

4}, Tahmina Rahman², Sarah Ennis¹

Affiliations

¹ University of Southampton, Southampton, UK.
² Wessex Kidney Centre, Portsmouth, UK.
³ Southampton Children's Hospital, Southampton, UK.
⁴ University Hospital Southampton NHS Foundation Trust, Southampton, UK.

Abstract

Dent disease type 1 is suspected in the presence of a complete phenotype of low molecular weight (LMW) proteinuria, hypercalciuria and at least one of the following: nephrocalcinosis, nephrolithiasis, haematuria, hypophosphatemia or chronic kidney disease (CKD). We present two brothers who presented with CKD alone. In the absence of typical clinical features, further assessment of LMW proteinuria and hypercalciuria was not undertaken. Whole-genome sequencing revealed hemizygous loss of function mutations in chloride voltage-gated channel 5 (CLCN5) consistent with Dent disease. Dent disease should, therefore, be considered in patients with an incomplete phenotype, including unexplained CKD alone.

Keywords: CLCN5; Dent disease; chronic kidney disease; nephrocalcinosis; nephrolithiasis.