This study describes the clinical presentation and diagnosis in all Danish patients (49, 41 unrelated) with Wilson disease (WND). On the basis of the number of diagnosed patients from 1990-2008, the prevalence was estimated to be 1:49 500. Among routinely used diagnostic tests, none were consistently indicative of WND, with the exception of the 24-h urine-Cu test, which is always outside the normal range. Mutations were identified in 100% of the screened ATP7B alleles (70 unrelated), including five novel mutations: p.1021K; p.G1158V; p.L1304F; IVS20-2A>G; Ex5_6del. In all, 70% of mutations were found in exons 8, 14, 17, 18, and 20. The most frequent mutation, p.H1069Q, comprised 18%. We propose a new and simple model that correlates genotype and age of onset. By assuming that the milder of two mutations is 'functionally dominant' and determines the age of onset, we classified 25/27 mutations as either severe (age of onset 20 years), and correctly predicted the age of onset in 37/39 patients. This method should be tested in other Wilson populations.
European Journal of Human Genetics, 2011, Vol 19, Issue 9, p. 935-41
Adenosine Triphosphatases; Adolescent; Adult; Age of Onset; Cation Transport Proteins; Child; Female; Genetic Association Studies; Hepatolenticular Degeneration; Humans; Incidence; Male; Mutation Rate; Prevalence; Journal Article; Research Support, Non-U.S. Gov't