ABCB11, ABCB4, ATP8B1, JAG1, TJP2
Inherited intrahepatic cholestasis is a heterogeneous group of disorders typically presenting as neonatal jaundice and leading to persistent liver dysfunction in children and adults. Although some of these conditions are associated with extrahepatic symptoms and varying laboratory and pathologic findings, there remains considerable clinical overlap between these disorders.
- Confirmation of diagnosis in a patient with chronic cholestasis of unknown etiology
- Screening for Alagille Syndrome
- Screening for Progressive Familial Intrahepatic Cholestasis (PFIC)
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.
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.
How to Order
Download Heritable Liver Disease requisition. Single gene sequencing, deletion/duplication analysis and targeted variant analysis is also available for all genes in the Jaundice Panel.
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