Relatively little is known about the relative impact of various mutations, although the H1069Q mutation seems to predict later onset and predominantly neurological problems, according to some studies. A comprehensive clinically annotated resource, WilsonGen provides clinical classification for the variants as per the recent ACMG & AMP guidelinesA normal variation in the PRNP gene can modify the course of the disease by delaying the age of onset and affecting the type of symptoms that develop. This gene produces prion protein, which is active in the brain and other tissues and also appears to be involved in transporting copper. A role for the ApoE gene was initially suspected but could not be confirmed.The condition is inherited in an autosomal recessive pattern. In order to inherit it, both of the parents of an individual must carry an affected gene. Most have no family history of the condition. People with only one abnormal gene are called carriers (heterozygotes) and may have mild, but medically insignificant, abnormalities of copper metabolism.Wilsons disease is the most common from a group of hereditary diseases that cause copper overload in the liver. All can cause cirrhosis at a young age. The other members of the group are Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis and idiopathic copper toxicosis. These are not related to ATP7B mutations: for example, ICC has been linked to mutations in the KRT8 and the KRT18 gene.
History
The disease bears the name of the British physician Samuel Alexander Kinnier Wilson (1878–1937), a neurologist who described the condition, including the pathological changes in the brain and liver, in 1912. Wilsons work had been predated by, and drew on, reports from German neurologist Carl Westphal (in 1883), who termed it "pseudosclerosis"; by the British neurologist William Gowers (in 1888); by the Finnish neuropathologist Ernst Alexander Homén (in 1889–1892), who noted the hereditary nature of the disease; and by Adolph Strümpell (in 1898), who noted hepatic cirrhosis. Neuropathologist John Nathaniel Cumings made the link with copper accumulation in both the liver and the brain in 1948. The occurrence of hemolysis was noted in 1967.In 1951, Cumings, and  New Zealand neurologist Derek Denny-Brown, working in the United States, simultaneously reported the first effective treatment, using metal chelator British anti-Lewisite . This treatment had to be injected but was one of the first therapies available in the field of neurology, a field that classically was able to observe and diagnose but had few treatments to offer. The first effective oral chelation agent, penicillamine, was discovered in 1956 by British neurologist John Walshe. In 1982, Walshe also introduced trientine, and was the first to develop tetrathiomolybdate for clinical use.