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Genetics of Wilson disease : A Comprehensive Overview

Wilson's disease is a genetic disorder characterized by an excess of copper stored in various body tissues, primarily the liver, brain, and eyes. This accumulation of copper leads to neurological or psychiatric symptoms and liver disease.

The genetic aspect of Wilson's disease lies in its autosomal recessive inheritance pattern. This means that an individual needs to inherit two copies of the defective gene, one from each parent, to develop the disease. If an individual receives only one copy of the faulty gene, they become carriers and generally do not show symptoms of the disease.

The ATP7B Gene

Wilson's disease is caused by mutations in the ATP7B gene located on chromosome 13. This gene encodes a protein, ATPase copper transporting beta (ATP7B), which is vital in the metabolism of copper in the body. Specifically, ATP7B is involved in the elimination of excess copper from the body and the incorporation of copper into ceruloplasmin, a protein that carries copper in the bloodstream.

Mutations in ATP7B

More than 500 different mutations in the ATP7B gene have been identified in people with Wilson's disease. These mutations disrupt the function of the ATP7B protein, impairing the body's ability to regulate copper transportation. Consequently, copper begins to accumulate in tissues, which leads to the various symptoms of Wilson's disease.

Genetic Testing

Genetic testing can identify mutations in the ATP7B gene, which can confirm a diagnosis of Wilson's disease, particularly in people with ambiguous clinical features. However, as there are many possible mutations and some are yet undiscovered, a negative genetic test doesn't necessarily rule out the disease.

The genetics of Wilson's disease involve the inheritance of two copies of a mutated ATP7B gene. This mutation disrupts the normal functioning of the ATP7B protein, causing copper to accumulate in the body. The ability to identify these mutations through genetic testing can aid in the diagnosis and management of this disease. However, due to the large number of potential mutations, genetic testing alone is not definitive in diagnosing Wilson's disease. It should be used in conjunction with clinical evaluation and other diagnostic tests.