Detection of DZIP1L mutations by whole-exome sequencing in consanguineous families with polycystic kidney disease
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Published:2022-02-24
Issue:11
Volume:37
Page:2657-2665
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ISSN:0931-041X
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Container-title:Pediatric Nephrology
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language:en
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Short-container-title:Pediatr Nephrol
Author:
Hertz Jens MichaelORCID, Svenningsen Per, Dimke Henrik, Engelund Morten Buch, Nørgaard Hanne, Hansen Anita, Marcussen Niels, Thiesson Helle Charlotte, Bergmann Carsten, Larsen Martin J.
Abstract
Abstract
Background
Autosomal recessive polycystic kidney disease is a cystic kidney disease with early onset and clinically characterized by enlarged echogenic kidneys, hypertension, varying degrees of kidney dysfunction, and liver fibrosis. It is most frequently caused by sequence variants in the PKHD1 gene, encoding fibrocystin. In more rare cases, sequence variants in DZIP1L are seen, encoding the basal body protein DAZ interacting protein 1-like protein (DZIP1L). So far, only four different DZIP1L variants have been reported.
Methods
Four children from three consanguineous families presenting with polycystic kidney disease were selected for targeted or untargeted exome sequencing.
Results
We identified two different, previously not reported homozygous DZIP1L sequence variants: c.193 T > C; p.(Cys65Arg), and c.216C > G; p.(Cys72Trp). Functional analyses of the c.216C > G; p.(Cys72Trp) variant indicated mislocalization of mutant DZIP1L.
Conclusions
In line with published data, our results suggest a critical role of the N-terminal domain for proper protein function. Although patients with PKHD1-associated autosomal recessive polycystic kidney disease often have liver abnormalities, none of the present four patients showed any clinically relevant liver involvement. Our data demonstrate the power and efficiency of next-generation sequencing-based approaches. While DZIP1L-related polycystic kidney disease certainly represents a rare form of the disease, our results emphasize the importance of including DZIP1L in multigene panels and in the data analysis of whole-exome sequencing for cystic kidney diseases.
Graphical abstract
A higher resolution version of the Graphical abstract is available as Supplementary information
Publisher
Springer Science and Business Media LLC
Subject
Nephrology,Pediatrics, Perinatology and Child Health
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