A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation.
Although both variants were predicted to be damaging to the mutant protein, only Y528C co-segregated with all of the PKD1-affected individuals in NFL10.
The rest of the patient samples also showed few variants in ADPKD (Autosomal Dominant Polycystic Kidney Disease) disease causing genes PKD1 and PKD2 i.e.
PKD1 and PKD2 variants were identified by direct gene sequencing and/or multiplex ligation-dependent probe amplification (MLPA) in 125 unrelated patients of ADPKD.
Technical Evaluation: Identification of Pathogenic Mutations in PKD1 and PKD2 in Patients with Autosomal Dominant Polycystic Kidney Disease by Next-Generation Sequencing and Use of a Comprehensive New Classification System.
To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases.ADPKD in this family is linked to PKD1.
In contrast, immortalized and primary cultured cyst-lining epithelial cells from ADPKD patients with mutations in PKD1 or with abnormal ciliary expression of polycystin-1 or -2 were not responsive to fluid shear stress.
Mutation-based molecular diagnostics of autosomal dominant polycystic kidney disease (ADPKD) is complicated by genetic and allelic heterogeneity, large multi-exon genes, and duplication sequences of PKD1.
In the present study, we have used a long-range polymerase chain reaction (PCR)-based strategy previously developed by our laboratory to analyze exons in the replicated region of PKD1 in a population of 41 unrelated Thai and 6 unrelated Korean families with ADPKD.
The phenotypic variability of autosomal dominant polycystic kidney disease (ADPKD) cannot be explained only by various mutations of two known genes (PKD1 and PKD2), but the influence of other unknown factors should also be considered.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in humans and is caused by mutations in the PKD1 or PKD2 gene.
To conclude, we demonstrated that selective CaSR activation in human ciPTEC carrying PKD1 mutation increases [Ca<sup>2+</sup>]<sub>i</sub>, reduces intracellular cAMP and mTOR activity, reversing the principal dysregulations considered the most proximal events in ADPKD pathogenesis, making CaSR a possible candidate as therapeutic target.