Evidence of a third ADPKD locus is not supported by re-analysis of designated PKD3 families.

Mutations to PKD1 and PKD2 are associated with autosomal dominant polycystic kidney disease (ADPKD). The absence of apparent PKD1/PKD2 linkage in five published European or North American families with ADPKD suggested a third locus, designated PKD3. Here we re-evaluated these families by updating clinical information, re-sampling where possible, and mutation screening for PKD1/PKD2.

Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease.

There are no proven, effective therapies for polycystic kidney disease (PKD) or polycystic liver disease (PLD). We enrolled 42 patients with severe PLD resulting from autosomal dominant PKD (ADPKD) or autosomal dominant PLD (ADPLD) in a randomized, double-blind, placebo-controlled trial of octreotide, a long-acting somatostatin analogue. We randomly assigned 42 patients in a 2:1 ratio to octreotide LAR depot (up to 40 mg every 28+/-5 days) or placebo for 1 year.

Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) caused by mutations in PKD1 is significantly more severe than PKD2. Typically, ADPKD presents in adulthood but is rarely diagnosed in utero with enlarged, echogenic kidneys. Somatic mutations are thought crucial for cyst development, but gene dosage is also important since animal models with hypomorphic alleles develop cysts, but are viable as homozygotes.

Characterization of large rearrangements in autosomal dominant polycystic kidney disease and the PKD1/TSC2 contiguous gene syndrome.

Large DNA rearrangements account for about 8% of disease mutations and are more common in duplicated genomic regions, where they are difficult to detect. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2. PKD1 is located in an intrachromosomally duplicated region.

Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic differences between MKS1 and MKS3.

Meckel-Gruber syndrome (MKS) is a recessively inherited, lethal disorder characterized by renal cystic dysplasia, occipital encephalocele, polydactyly and biliary dysgenesis. MKS is genetically heterogeneous with three loci mapped and two identified; MKS1 (17q23) and MKS3 (8q22.1).