ADPKD is caused by mutations in either <i>PKD1</i> or <i>PKD2</i> genes that encode for integral membrane proteins Polycystin-1 (PC1) and Polycystin-2 (PC2), respectively.
Autosomal dominant polycystic kidney disease (ADPKD), the commonest inherited kidney disease, is generally caused by heterozygous mutations in PKD1, PKD2, or GANAB (PKD3).
Mutations in the gene (pkd2) encoding polycystin-2 (PC2) are associated with autosomal dominant polycystic kidney disease (ADPKD), the most common inherited nephropathy.
This study demonstrates the effectiveness of NGS in significantly reducing the cost and time for simultaneous sequence analysis of PKD1 and PKD2, simplifying the genetic diagnostics of ADPKD.
Although altered intracellular trafficking of PC1 and PC2 is an underlying feature of ADPKD, the mechanisms which govern vesicular transport of the polycystins through the biosynthetic and endosomal membrane networks remain to be fully elucidated.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, potentially lethal, monogenic diseases and is caused predominantly by mutations in polycystic kidney disease 1 (PKD1) and PKD2, which encode polycystin 1 (PC1) and PC2, respectively.
We introduce a novel method for measuring heterologous polycystin-2 channels in cilia, which will have utility in characterizing <i>PKD2</i> variants that cause ADPKD.
Using targeted next-generation sequencing of 65 candidate genes in a patient with an ADPKD-like phenotype who lacked the familial PKD2 mutation, we identified a COL4A1 mutation (p.Gln247*) and made the diagnosis of HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome.
Mutations in polycystin-1 (PC1) and polycystin-2 (PC2) result in a commonly occurring genetic disorder, called Autosomal Dominant Polycystic Kidney Disease (ADPKD), that is characterized by the formation and development of kidney cysts.
Autosomal dominant polycystic kidney disease (ADPKD), caused by PKD1 and PKD2 gene mutations, is one of the most common genetic diseases, affecting up to 1 in 500 people.
ADPKD is caused by mutation in one of two genes-85% of cases are caused by mutation in PKD1 on chromosome 16 and 15% of cases are caused by mutation in PKD2 on chromosome 4.
In addition, we further found that rapamycin arrested aberrant epithelial-cell proliferation in the ADPKD kidney by down-regulating the cell-cycle-associated cyclin-dependent kinase 1 (CDK1) and cyclins, namely cyclin A, cyclin B, cyclin D1 and cyclin E, demonstrating a direct link between mTOR signalling changes and the polycystin-2 dysfunction in cystogenesis.
We investigated miRNA-mediated regulatory systems and networks that play an important role during cystogenesis through integrative analysis of miRNA- and RNA-seq using two ADPKD mouse models (conditional Pkd1- or Pkd2-deficient mice), at three different time points (P1, P3, and P7).
Finally, we propose novel strategies for uncovering the mode of action of PC1 and PC2 and suggest means by which their dysfunction or loss of expression lead to cystogenesis and ADPKD development.
Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disorder that is caused by mutations in the genes PKD1 and PKD2 encoding polycystin-1 and polycystin-2, respectively.