Disease
Progressive familial intrahepatic cholestasis 3, benign recurrent intrahepatic cholestasis 3, MDR3 deficiency
Description
Variants in ABCB4 are associated with progressive familial intrahepatic cholestasis (PFIC3) which is inherited as an autosomal recessive condition. The main clinical features of PFIC3 are hepatomegaly, cholestasis, pruritus, elevated serum bile acids, and high GTP (GGT). Variants in the ABCB4 gene also cause other MDR3-related conditions such as intrahepatic cholestasis of pregnancy and low phospholipids-associated cholelithiasis.
Indications
- Screening for Progressive Familial Intrahepatic Cholestasis (PFIC)
- Benign recurrent intrahepatic cholestasis 3
- MDR3 deficiency
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
Van der Woerd, W.L., S.W.C. van Mil, et al. (2010) "Familial Cholestasis: Progressive Familial Intrahepatic Cholestasis, Benign Recurrent Intrahepatic Cholestasis and Intrahepatic Cholestasis of Pregnancy." Best Practice & Research. Clinical Gastroenterology 24(5): 541-53.
