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Pediatric Nephrology
Published in: Pediatric Nephrology 9/2019

01-09-2019 | Polycystic Kidney Disease | Original Article

Bialleleic PKD1 mutations underlie early-onset autosomal dominant polycystic kidney disease in Saudi Arabian families

Authors: Mohamed H. Al-Hamed, Nada Alsahan, Sarah J. Rice, Noel Edwards, Eman Nooreddeen, Maha Alotaibi, Wesam Kurdi, Maha Alnemer, Naderah Altaleb, Wafa Ali, Nouf Al-Numair, Najd Almejaish, John A. Sayer, Faiqa Imtiaz

Published in: Pediatric Nephrology | Issue 9/2019

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Abstract

Background

Polycystic kidney disease (PKD) is one of the most common genetic renal diseases and may be inherited in an autosomal dominant or autosomal recessive pattern. Pathogenic variants in two major genes, PKD1 and PKD2, and two rarer genes, GANAB and DNAJB11, cause autosomal dominant PKD (ADPKD). Early onset and severe PKD can occur with PKD1 and PKD2 pathogenic variants and such phenotypes may be modified by second alleles inherited in trans. Homozygous or compound heterozygous hypomorphic PKD1 variants may also cause a moderate to severe disease PKD phenotype.

Methods

Targeted renal gene panel followed by Sanger sequencing of PKD1 gene were employed to investigate molecular causes in early onset PKD patients.

Results

In this study, we report four consanguineous Saudi Arabian families with early onset PKD which were associated with biallelic variants in PKD1 gene.

Conclusions

Our findings confirm that PKD1 alleles may combine to produce severe paediatric onset PKD mimicking the more severe autosomal recessive ciliopathy syndromes associated with PKD. Screening of parents of such children may also reveal subclinical PKD phenotypes.
Appendix
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Metadata
Title
Bialleleic PKD1 mutations underlie early-onset autosomal dominant polycystic kidney disease in Saudi Arabian families
Authors
Mohamed H. Al-Hamed
Nada Alsahan
Sarah J. Rice
Noel Edwards
Eman Nooreddeen
Maha Alotaibi
Wesam Kurdi
Maha Alnemer
Naderah Altaleb
Wafa Ali
Nouf Al-Numair
Najd Almejaish
John A. Sayer
Faiqa Imtiaz
Publication date
01-09-2019
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 9/2019
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-019-04267-x

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