The Wilson disease gene: spectrum of mutations and their consequences

Abstract

We have previously reported the cloning of a gene that encodes a copper transporting P-type ATPase (ATP7B) which is defective in Wilson disease. We have now identified in 58 WND patients, 20 new mutations as well as three of five previously published mutations: 11 small insertions and deletions, seven missense, two nonsense and three splice site mutations. Two of the mutations are relatively frequent, representing 38% of the mutations in patients of European origin. Our findings suggest a wider spectrum of age of onset than is considered typical of Wilson disease: mutations that completely disrupt the gene can produce liver disease in early childhood when Wilson disease may not typically considered in the differential diagnosis. The mutations identified provide an explanation for at least part of the wide phenotypic variation observed in Wilson disease.

Liver transplantation for wilson's disease: A single-center experience

“…[1][2][3][4][5][6][22][23][24] This leads to the toxic accumulation of copper in the liver and other organs, such as the brain, kidneys, and corneas. Medical therapy with chelating agents has proven effective in controlling the disease progression and is effective in the prevention of central nervous system complications.…”

“…[3][4][5] The disease is characterized by excessive deposition of copper throughout the body, predominantly in the liver, brain, cornea, and kidneys. Severity and time of presentation of the liver disease or neurological manifestations or sex preponderance could be related to gene mutations.…”

“…Severity and time of presentation of the liver disease or neurological manifestations or sex preponderance could be related to gene mutations. 5,6 Thus far, more than 60 mutations throughout the gene have been reported. 5 The most common presentation of this disease is with neurological symptoms in adolescents and young adults and signs of progressive hepatic decompensation.…”

“…5,6 Thus far, more than 60 mutations throughout the gene have been reported. 5 The most common presentation of this disease is with neurological symptoms in adolescents and young adults and signs of progressive hepatic decompensation. 2 Medical therapy with chelating agents has proven to be an effective treatment for Wilson' s disease, leading to remarkable improvement and resolution of symptoms, even in rather advanced conditions.…”

Cloning and Characterization of the Promoter Region of the Wilson Disease Gene

“…Several mutations have been reported in WD and MNK patients since their structural genes were identified in 1993 (8)(9)(10). Characterization of the promoter region of the WD gene in depth should reveal whether the WD gene is also regulated by iron metabolism.…”