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Semin Liver Dis 2011; 31(3): 233-238
DOI: 10.1055/s-0031-1286054
© Thieme Medical Publishers

Clinical Molecular Diagnosis of Wilson Disease

James Bennett1 , Si Houn Hahn1 , 2
  • 1Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle Children's Hospital, Seattle, Washington
  • 2Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Hospital, Seattle, Washington
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Publication History

Publication Date:
07 September 2011 (online)

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ABSTRACT

Wilson disease is an autosomal recessive disorder of copper transport characterized by toxic accumulation of copper in the liver, brain, and other organs. It is lethal if untreated, but effective treatment is available. The broad spectrum of clinical manifestations, including hepatic and neuropsychiatric symptoms, can present over a large age range, contributing to difficulty in recognition of this disease. The diagnosis has traditionally rested on measurements of ceruloplasmin and copper in urine and liver, but it remains a challenge due to ambiguous biochemical results that can overlap with healthy carriers. Although hepatic copper concentration has been the gold standard for diagnosis, direct sequencing of the ATP7B gene is sensitive, specific, and can obviate the need for invasive liver biopsy. In this article, the authors review the sensitivity, limitations, and pitfalls of ATP7B sequencing in the diagnosis of Wilson disease. ATP7B sequencing should be standard practice in the diagnosis of Wilson disease.

KEYWORDS

Wilson disease - genetic testing - molecular diagnosis - mutation spectrum - sensitivity

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Sihoun Hahn M.D. Ph.D. 

Professor, Department of Pediatrics, University of Washington School of Medicine

Seattle Children's Hospital, 4800 Sand Point Way, B6594, Seattle, WA 98105

Email: sihahn@uw.edu