Variants in ATP7B are associated with Wilson Disease, which is inherited as an autosomal recessive condition. Wilson Disease is characterized by high levels of intracellular hepatic copper resulting in hepatic disease and neurologic abnormalities. The ATP7B gene encodes the protein copper-transporting ATPase 2, which is found primarily in the liver and is important for removal of surplus copper from the body. Wilson disease (WD) has a variable phenotype and is due to excessive toxic copper accumulation in body tissues, specifically the liver and central nervous system. Hepatic symptoms typically present in first decades of life with jaundice, fatigue, loss of appetite, and abdominal swelling. Neurological manifestations present later in life with tremors, clumsiness, impaired thinking, anxiety, and speech problems. Wilson Disease is a progressive condition that can be fatal if left untreated.
Low ceruloplasmin serum levels
Low serum concentration of copper and non-ceruloplasmin-bound copper
High urinary copper
High liver copper concentration
Kayser-Fleischer ring on the cornea
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. Targeted variant analysis and deletion/duplication analysis is also available for ATP7B.
Aggarwal, A. and M. Bhatt (2013) "Update on Wilson Disease." International Review of Neurobiology 110: 313-48.
Ferenci, P. (2004) "Pathophysiology and Clinical Features of Wilson Disease." Metabolic Brain Disease 19(3-4): 229-39.
Rosencrantz, R. and M. Schilsky (2011) "Wilson Disease: Pathogenesis and Clinical Considerations in Diagnosis and Treatment." Seminars in Liver Disease 31(3): 245-59.
Tanzi, R.E., K. Petrukhin, et al. (1993) "The Wilson Disease Gene Is a Copper Transporting ATPase with Homology to the Menkes Disease Gene." Nature Genetics 5(4): 344-50.
Thomas, G.R., J.R. Forbes, et al. (1995) "The Wilson Disease Gene: Spectrum of Mutations and Their Consequences." Nature Genetics 9(2): 210-7.
Weiss, K.H. (2016) “Wilson Disease” Gene Reviews. Accessed on Sept 24, 2018 at https://www.ncbi.nlm.nih.gov/books/NBK1512/.