Wilson Disease / Hepatolenticular Degeneration via the ATP7B Gene

Wilson disease (WD, OMIM 277900), also called hepatolenticular degeneration, is a disorder of copper metabolism. WD results from the toxic accumulation of copper, mainly in the liver, brain, kidneys, and eyes. WD is characterized by an extensive clinical variability between individuals with regards to age of onset, severity, and clinical presentation. The hallmarks of WD include a gold-brown ring (Kayser-Fleischer ring) around the edge of the iris and in the rim of the cornea, reduced serum levels of ceruloplasmin, and elevated urinary copper excretion. Depending on which organ systems are affected, symptoms may also include jaundice, enlargement of the liver or spleen, fatigue, seizures, slurred speech, difficulty swallowing, tremor, dystonia, personality changes, depression, and psychosis. Age of onset varies between three and seventy years of age. WD occurs worldwide, with an estimated incidence between 1:30,000 and 1:100,000 (Ala et al. Lancet 369:397-408, 2007; de Bie et al. J Med Genet 44:673-688, 2007). It is, however, most common in the Sardinian population.

Wilson Disease (WD) is inherited with an autosomal recessive manner and results from variants in the ATP7B gene (Bull et al. Nat Genet 5:327-337, 1993; Tanzi et al. Nat Genet 5:344-350, 1993). Over 500 variants have been detected in patients with WD, most of which are missense/nonsense, small insertions/deletions and splicing. Gross insertions, deletions and complex rearrangements are rare. Although most WD-causing variants are found only in single families, three variants are prevalent. These are the H1069Q substitution in European and North American populations, the R778L substitution in Southeast Asia (Ferenci Hum Genet 120:151-159, 2006), and a 15-bp deletion in the gene promoter in the Sardinian population (Loudianos et al. Hum Mutat 14:294-303, 1999). The ATP7B gene encodes an ATPase which participates in the transport of copper ions across membranes.

This test detects variants in about 98% of individuals with WD (Cox and Roberts, GeneReviews, 2006).

This test provides full coverage of all coding exons of the ATP7B gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.