Bialleleic PKD1 mutations underlie early-onset autosomal dominant polycystic kidney disease in Saudi Arabian families.
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.
['Al-Hamed|Mohamed H|MH|0000-0002-7207-6122', 'Alsahan|Nada|N|', 'Rice|Sarah J|SJ|', 'Edwards|Noel|N|', 'Nooreddeen|Eman|E|', 'Alotaibi|Maha|M|', 'Kurdi|Wesam|W|', 'Alnemer|Maha|M|', 'Altaleb|Naderah|N|', 'Ali|Wafa|W|', 'Al-Numair|Nouf|N|', 'Almejaish|Najd|N|', 'Sayer|John A|JA|', 'Imtiaz|Faiqa|F|']
D017668:Age of Onset D002648:Child D003198:Computer Simulation D003241:Consanguinity D004252:DNA Mutational Analysis D005260:Female D006720:Homozygote D006801:Humans D007668:Kidney D008297:Male D009154:Mutation D016891:Polycystic Kidney, Autosomal Dominant D012529:Saudi Arabia D050396:TRPP Cation Channels D014463:Ultrasonography
PKD1 ADPKD Consanguinity Biallelic mutations Molecular genetics