Wilson's Disease: A Genetic Analysis

Introduction
Wilson’s disease is an inherited copper metabolism disorder that results in neurological, hepatic or psychiatric problems (Das & Ray, 2006; Ferenci, 2004; Patil, et al., 2013). It is a genetic disorder which is fatal if copper poisoning starts developing and illness becomes serious. It is also fatal if not properly diagnosed or treated. Excess copper begins to accumulate in liver, brain and other tissues due to this genetic defect. Dr. Samuel Alexander Kinnier Wilson was the first to describe this condition in 1912. Since its discovery many studies have been conducted to reveal its associated genetic and biochemical abnormalities and disturbances. This genetic disorder follows autosomal recessive pattern of inheritance.

Copper

It is the only affected organ in about half of the patients. The individuals must be tested for Wilson’s disease with unexplained abnormal liver tests. The changes that initially occur in liver are visible only through microscope. Patients often actually have Wilson’s disease hepatitis when they thought to have infectious hepatitis or infectious mononucleosis. The brain generally affects symmetrically with excessive deposition of copper but one side of body gets more affected as compared to another showing factor of asymmetric neurological development such as being left or right handed. Basal ganglion is the area deep within brain that is responsible for coordination of movements. The copper is most prominently seen in basal ganglia. The characteristic appearance of the basal ganglia in advanced Wilson’s disease is the face of the giant panda

A multi-ethnic distribution is observed in Wilson’s disease but a higher prevalence of the H1069Q mutation has been described in central Europe. Mutations in exons 8 and 15 are also common among over 150 described mutations in ATP7B gene. This point mutation is originated from a single founder in Eastern Europe and is frequent in affected patients of Hungary. Besides this, the uncommon mutations in Hungarian patients are mutations in exons 8, 13, 15 and 18. About 50-80% of affected individuals carry at least one allele of this mutation with frequency ranging between 30-70%. The allele frequency of other mutations is less than 10%; those mutations are located on exons 8, 15 and 13. Neurological features predominantly and late age of onset is observed in Slavic type, an ethnic group in Europe. Juvenile type is another ethnic group which occurs in Western Europe has onset before 16 years of age and mainly has hepatic presentation during the disease. Data from non-European countries are