Gene Symbol: PKD1
Chromosomal Locus 16p13.3
Pseudonyms: Adult Polycystic Kidney Disease (APKD), Autosomal Dominant Polycystic Kidney Disease (ADPKD)
TURNAROUND TIME: 3 weeks
TESTING METHODOLOGY: Polymerase chain reaction (PCR) of highly variable microsatellite regions within and adjacent to the PKD1 gene (markers included are KG8, D16S283, D16S291, D16S521, D16S475). As a linkage test several family members need to be tested. Please call the laboratory for details and see Special Requirement below.
- Collect: Prefer two 5ml whole blood EDTA (lavender top) tube.
- Min. Collection: 0.7 ml whole blood EDTA.
- Transport: blood EDTA at Room Temp shipped regular next day air (No Saturday delivery; store specimen refrigerated and ship Monday).
- Stability: Ambient: up to 7 days; Refrigerated: 2 weeks. Frozen: unacceptable
- Unacceptable Conditions: Serum. Frozen or severely hemolyzed blood. Clotted blood.
Prenatal testing: Direct: 5ml direct unspun amniotic fluid or 15mg CVS tissue with a backup flask growing. Culture: confluent T25 flask. Maternal blood sample is required for maternal cell contamination studies.
Counseling and informed consent are recommended for genetic testing. A consent form
is available as a resource but not required.
A family pedigree is required with submission of specimen(s). Since this a linkage test several family members must be tested. Typically, 3 -8 family members are tested as a single unit. However, samples can be collected from family members at different sites and collated at the laboratory. It is suggested a pedigree be collected and then confer with our laboratory for details and strategy. The study is charged as a single test even though there are multiple family members in the analysis.
Incidence: ADPKD incidence is between 1 in 400 - 1000 live births and is the most common lethal autosomal dominant disease. ADPKD is caused by PKD1 (85%) and PKD2 (15%) genes and is one of the most common reasons for renal failure and kidney transplant.
Inheritance: Autosomal dominant. Highly penetrant.
Disease Characteristics: Autosomal dominant polycystic kidney disease (ADPKD) is generally a late-onset multisystem disorder characterized by bilateral renal cysts; vascular abnormalities including intracranial aneurysms, dilatation of the aortic root,and dissection of the thoracic aorta. Hypertension, renal pain, and renal insufficiency are common. Half of the individuals with ADPKD have end-stage renal disease by age 60. On the other hand, early hypertension is often a result of undiagnosed ADPKD.
Molecular Genetic Mechanism: Linkage can both predict the risk of the condition as well as differentiate between PKD1 and PKD2. However, multiple family members are required. Microsatellite variations within the PKD1 gene region are used as markers to trace the disease associated gene through the family. Therefore, it eliminates the necessity of actually detecting the disease causing mutation.
Clinical Sensitivity: 85% for the PKD1 gene. Combined with PKD2 gene testing (15% incidence) the clinical sensitivity is near 100%. Therefore, in most cases, both linkage tests are performed.
Analytical Sensitivity: 99%.
- The most significant limitation is that linkage generally requires 3 or more family members to participate in the study. Isolated cases are left with sequencing as their only option.
- Uninformativeness for some of the microsatellite loci.
- Occasional recombination within the gene.
- Rare diagnostic errors can occur due to primer or probe site mutations or rare polymorphisms.
INDICATIONS FOR USE:
- To confirm a clinical diagnosis.
- To differentiate PKD1 from PKD2 patients.
- To determine whether an individual is a candidate as a donor for a kidney transplant to another family member. To help clarify the cause of early onset hypertension.