Autosomal dominant polycystic kidney disease (ADPKD) is primarily caused by mutations in polycystin 1, transient receptor potential channel interacting (PKD1) and PKD2, and characterized by numerous cysts in various organs, primarily the kidneys and liver.
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited monogenic renal disease characterised by the accumulation of clusters of fluid-filled cysts in the kidneys and is caused by mutations in PKD1 or PKD2 genes.
An affected son, but not the mother, in the Italian family had the nonsense mutation PKD1: p.R4228X, which appeared de novo in the son, with simple cysts probably explaining the mother's phenotype.
A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation.
The demonstration of loss of heterozygosity for PKD1 and the absence of immunoreactive polycystin 1 in approximately 20% of the cysts supports a two-hit tumor suppressor gene model of cystogenesis.
Finally, the occurrence of typical renal and extrarenal signs of ADPKD in a PKD1 hemizygote individual seems to support concept that a somatic inactivation of the residual PKD1 gene is required for the development of the cysts.
Pkd1- heterozygotes have no discernible phenotype, whereas homozygotes die during the perinatal period with massively enlarged cystic kidneys, pancreatic ductal cysts and pulmonary hypoplasia.
All subjects over the age of 30 years carrying a mutation at the PKD1 locus showed renal ultrasonographic cysts, but 40% of carriers of the PKD1 mutation younger than 30 years did not have renal cysts.
The mean (+/- SE) age at the onset of end-stage renal disease among members of the PKD1 families was 56.7 +/- 1.9 years, as compared with 69.4 +/- 1.7 years among members with cysts in the families without linkage (P = 0.0025).
In patients with RCC and pulmonary cysts but without cutaneous lesions, screening for mutations in the FLCN gene should be performed, especially for those with a family history of RCC or pulmonary cysts (pneumothorax).
Folliculin (FLCN) is the tumor suppressor associated with Birt-Hogg-Dubé (BHD) syndrome that predisposes patients to incident of hamartomas and cysts in multiple organs.
A rare mutation of the folliculin gene was detected in the patient and members with pulmonary cysts or pneumothorax, but no skin or renal lesions were found.
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited monogenic renal disease characterised by the accumulation of clusters of fluid-filled cysts in the kidneys and is caused by mutations in PKD1 or PKD2 genes.
Autosomal dominant polycystic kidney disease (ADPKD) is primarily caused by mutations in polycystin 1, transient receptor potential channel interacting (PKD1) and PKD2, and characterized by numerous cysts in various organs, primarily the kidneys and liver.