Disease

Progressive familial intrahepatic cholestasis 4

Description

Variants in TJP2 are associated with progressive familial intrahepatic cholestasis (PFIC4), which is inherited as an autosomal recessive condition. PFIC4 leads to abnormal bile formation and elevated serum bile acids. Patients typically present in infancy or childhood with hepatomegaly, coagulopathy, cholestasis, and pruritus. Patients may progress to end-stage liver disease before adulthood.

Indications

  • Progressive familial intrahepatic cholestasis

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 gene(s) 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

Testing for this gene is available as part of the Liver Disease Panel and Jaundice Panel by next-generation sequencing. Single gene sequencing, deletion/duplication analysis and targeted variant analysis is also available for this gene. Download Heritable Liver Disease requisition.

References

Carlton, V.E.H., B.Z. Harris, et al. (2003) "Complex Inheritance of Familial Hypercholanemia with Associated Mutations in TJP2 and BAAT." Nature Genetics 34(1): 91-6.

Sambrotta, M., Strautnieks, S., et al. (2014) “Mutations in TJP2 cause progressive cholestatic liver disease." Nature genetics 46(4): 326-8.

Van Mil S.W. et al. (2005) "Genetics of familial intrahepatic cholestasis syndromes." J Med Genet 42(6):449-63.