Genes Tested:

ALG8, DNAJB11, DZIP1L, GANAB, LRP5, PKD2, PKHD1, PRKCSH, SEC63

Description

Polycystic liver disease with or without kidney cysts is usually inherited as autosomal dominant condition and becomes apparent in adulthood. Symptoms can range from asymptomatic to obstructive issues and complications such as intracystic hemorrhage, portal infection or rupture of cysts. Only a subset of patients develop kidney cysts, which usually incidental and do not result in clinically significant renal disease.

Polycystic kidney disease with or without liver disease may be inherited as an autosomal dominant or recessive condition. Presentation varies depending on the causative gene, ranging from neonatal period to adulthood. End-stage renal disease (ESRD) is a common complication in most of these conditions.

Indications

  • Presence of cysts in the liver or kidney
  • Family history of liver and/or kidney cysts

  • Cysts in liver or kidney with an abnormality of extra hepatic bile ducts

Testing Methodology

This test is performed by enrichment of the coding exons, flanking intronic and untranslated regions (5’ and 3’), as well as known pathogenic variants (HGMD 2018.1) in the promoter and deep intronic regions of the genes specified above using oligonucleotide probe hybridization followed by next-generation sequencing with >50X coverage at every target base. All pathogenic and novel variants, as well as variants of unknown (indeterminate) significance, as determined bioinformatically, are confirmed by Sanger sequencing. Regions with <50X will be filled in by Sanger sequencing. A detailed non-coding variant list is available upon request.

Test Sensitivity

Analytical Sensitivity: The sensitivity of DNA sequencing is over 99% for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed.

Limitations: Variants in regulatory regions and non-reported variants in untranslated regions may not be detected by this test. Large deletions involving entire single exons or multiple exons, large insertions and other complex genetic events will not be identified using NGS methodology. Rare primer site variants may lead to erroneous results.

Turnaround Time

28 days

How to Order

Download Heritable Liver Disease requisition. Single gene sequencing and targeted variant analysis is also available for all genes in the Cystic Disease of the Liver/Kidney Panel. Deletion/Duplication analysis is also available for the ALG8, LRP5, PKD2, and PRKCSH genes.

References

Bergmann, C. (2015) "ARPKD and Early Manifestations of ADPKD: The Original Polycystic Kidney Disease and Phenocopies." Pediatric Nephrology (Berlin, Germany) 30(1): 15-30.

Cnossen, W.R. and J.P.H. Drenth (2014) "Polycystic Liver Disease: An Overview of Pathogenesis, Clinical Manifestations and Management." Orphanet Journal of Rare Diseases 9: 69.

Cornec-Le Gall, E., V.E. Torres, et al. (2018) “Genetic complexity of autosomal dominant polycystic kidney and liver diseases.” Journal of American Society of Nephrology 29:13-23.

Drenth, J.P., R.H. te morsche, et al. (2003) "Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease." Nat Genet 33(3): 345-7.

Gevers, T.J.G. and J.P.H. Drenth (2013) "Diagnosis and Management of Polycystic Liver Disease." Nature Reviews. Gastroenterology& Hepatology 10(2): 101-8.

Guay-Woodford, L.M. (2014) "Autosomal Recessive Polycystic Kidney Disease: The Prototype of the Hepato-Renal Fibrocystic Diseases." Journal of Pediatric Genetics 3(2): 89–101.

Li, A., S. Davila, et al. (2003) "Mutations in PRKCSH Cause Isolated Autosomal Dominant Polycystic Liver Disease." American Journal of Human Genetics 72(3): 691-703.

Verghese, P. and Y. Miyashita (2014) "Neonatal Polycystic Kidney Disease." Clinics in Perinatology 41(3): 543-60.