A novel deletion mutation within the carboxyl terminus of the copper-transporting ATPase gene causes Wilson disease

In patients with Wilson disease (WD), an autosomal recessive disorder, toxi c accumulation of copper results in fatal liver disease and irreversible ne uronal degeneration. ATP7B, the gene mutated in WD, contains 21 exons and e ncodes a copper-transporting ATPase, in this study all exons of the ATP7B g ene of nine WD patients were screened for alterations by conventional mutat ion detection enhancement (MDE) heteroduplex analysis, followed by direct s equencing of the regions that showed heteroduplex formation. For the first time, a novel deletion mutation (4193delC) in exon 21, causing a frameshift leading to premature truncation of the protein was detected in four of nin e patients. The 4193delC removes several signals within the carboxyl termin al domain that may disrupt trafficking of ATP7B protein through trans-Golgi network at the cellular level. (C) 2000 Published by Elsevier Science B.V.