We tested linkage or non-linkage to the closely linked DNA markers flanking the PKD1 (D16S663 and D16S291) and one intragenic D16S3252 and PKD2 (D4S1563 and D4S2462) in 30 ADPKD-affected families, to determine the distributions of alleles and the degree of microsatellite polymorphisms (in 91 patients and 125 healthy subjects).
Patients with autosomal dominant polycystic kidney disease (ADPKD) typically carry a mutation in either the PKD1 or PKD2 gene, which leads to massive cyst formation in both kidneys.
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.
Moreover, Pkd2(-/-) mice with homozygous PKD2(tg)-transgene alleles (Pkd2(-/-);PKD2(tg/tg)) showed significant further amelioration of the cystic severity compared to that in Pkd2(-/-) mice with a hemizygous PKD2(tg) allele (Pkd2(-/-);PKD2(tg)), suggesting that the ADPKD phenotype was improved by increased transgene dosage.
Low bone turnover osteopenia has been reported in mice with conditional deletion of the PKD1 and PKD2 genes in osteoblasts, and preliminary clinical data also suggest suppressed bone turnover in patients with ADPKD.
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.
This review focuses on the molecular assembly, function, and regulation of TRPP2 as a cell surface cation channel and discusses its potential role in Ca(2+) signaling and ADPKD pathophysiology.
We show that confluent primary ADPKD cyst cells with the novel PC1 mutation DeltaL2433 and with normal abundance of PC1 and PC2 polypeptides lack ciliary PC1 and often lack ciliary PC2, whereas PC1 and PC2 are both present in cilia of confluent normal human kidney (NK) epithelial cells in primary culture.
Therefore, the model Pkd2(WS25/-), which carries the WS25 unstable allele and a true null allele, produces somatic second hits during mouse development or adult life and establishes an extremely faithful model of human ADPKD.
Here, we report a follow-up study of a unique multigeneration family with bilineal ADPKD (NFL10) in which a PKD1 disease haplotype and a PKD2 (L736X) mutation co-segregated with 18 and 14 affected individuals, respectively.
Although disease-causing mutations have been found in two genes, PKD1 and PKD2, a small number of ADPKD families exist that are unlinked to either of these genes, suggesting involvement of a third, as yet unidentified PKD3 gene.
Mutations in PKD1 and PKD2, the genes encoding the proteins polycystin-1 (PC1) and polycystin-2 (PC2), cause autosomal dominant polycystic kidney disease (ADPKD).