ABCB11, ABCB4, ABCC12, ABCC2, ABCD3, ABCG5, ABCG8, AKR1D1, ALDOB, AMACR, ATP7B, ATP8B1, BAAT, CC2D2A, CFTR, CLDN1, CYP27A1, CYP7A1, CYP7B1, DCDC2, DGUOK, DHCR7, EHHADH, EPHX1, FAH, GPBAR1, HNF1A, HNF1B, HSD17B4, HSD3B7, INVS, JAG1, LIPA, MKS1, MPV17, MYO5B, NEUROG3, NOTCH2*, NPC1, NPC2, NPHP1, NPHP3, NPHP4, NR1H4, PEX1, PEX10, PEX11B, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6, PEX7, POLG, SCP2, SERPINA1, SLC10A1, SLC10A2, SLC25A13, SLC27A5, SMPD1, TJP2, TMEM216, TRMU, UGT1A1, VIPAS39, VPS33B
*excluding exons 1, 2, and 4 in NOTCH2 due to high homologous regions
The Liver Disease Panel is designed to diagnose the most common genetic causes of hereditary liver disease. Inherited liver disease can present with clinical features including bile acid synthesis defects, cholestasis, and jaundice. Hereditary liver disease is caused by variants in many different genes, and may be inherited in an autosomal dominant or autosomal recessive manner.
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. Exons 1, 2, and 4 of the NOTCH2 gene are not covered by this test due to high homologous regions.
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 and targeted variant analysis is also available for all genes in the Liver Disease Panel. Deletion / Duplication analysis is also available for many of the genes on this panel. Learn more about genes available for deletion / duplication analysis.
Amer, S., A. Hajira. "A comprehensive review of progressive familial intrahepatic cholestasis (PFIC): genetic disorders of hepatocanalicular transporters." Gastroenterology research 7.2 (2014): 39.
Carey, E.J., A.H. Ali, et al. (2015) “Primary Biliary Cirrhosis.” Lancet (London, England) 386(10003): 1565-75.
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.
Devictor, D., P. Tissieres, et al. (2011) “Acute Liver Failure in Children.” Clinics and Research in Hepatology and Gastroenterology 35(6-7): 430-7.
Erlinger, S. (2015) “NTCP Deficiency: A New Inherited Disease of Bile Acid Transport.” Clinics and Research in Hepatology and Gastroenterology 39(1): 7-8.
Guegan, K., K. Stals, et al. (2012) “JAG1 Mutations Are Found in Approximately One Third of Patients Presenting with Only One or Two Clinical Features of Alagille Syndrome.” Clinical Genetics 82(1): 33-40.
Herbst, S. M., et al. "Taking the next step forward–diagnosing inherited infantile cholestatic disorders with next generation sequencing." Molecular and cellular probes 29.5 (2015): 291-298.
Komatsu, M., M. Yazaki, et al. (2008) “Citrin Deficiency as a Cause of Chronic Liver Disorder Mimicking Non-Alcoholic Fatty Liver Disease.” Journal of Hepatology 49(5): 810–20.
Morotti, R.A., F.J. Suchy, et al. (2011) “Progressive Familial Intrahepatic Cholestasis (PFIC) Type 1, 2, and 3: A Review of the Liver Pathology Findings.” Seminars in Liver Disease 31(1): 3–10.
Pham, D., Kudira, R. et al. (2021) "Deleterious Variants in ABCC12 are Detected in Idiopathic Chronic Cholestasis and Cause Intrahepatic Bile Duct Loss in Model Organisms." Gastroenterology 161(1):287-300.
Shagrani, M., et al. "Genetic profiling of children with advanced cholestatic liver disease." Clinical genetics 92.1 (2017): 52-61.
Togawa, Takao, et al. "Molecular genetic dissection and neonatal/infantile intrahepatic cholestasis using targeted next-generation sequencing." The Journal of pediatrics 171 (2016): 171-177.
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.
Van Mil, S.W.C., R.H.J. Houwen, et al. (2005) “Genetics of Familial Intrahepatic Cholestasis Syndromes.” Journal of Medical Genetics 42(6): 449–63.