Mutation screening and genotype-phenotype correlation in 32 families with Wilson disease

Wilson disease (WD) is an autosomal recessive disorder of copper transport, manifesting as chronic liver disease and/or neurologic impairment due to a ccumulation of copper in several tissues, principally the liver and the bra in. The WD gene encodes a copper transporting P-type ATPase that is defecti ve in this affection. In this study, we performed DNA haplotype analysis us ing five polymorphic microsatellite markers (D13S295, D13S314, D13S301, D13 S296, D13S316) flanking the WD locus, mutational screening on 10 exons (5, 7, 8, 9, 12, 14, 15, 17, 18, 19) by SSCP and direct sequencing in 32 WD fam ilies with hepatic and/or neurologic forms. We found nine mutations (two fr ameshifts, one nonsense, five missense mutations, and one in an intron), fo ur of which were novel. The data were used to make presymptomatic diagnosis and detect carriers among siblings in the pedigrees concerned, improving g enetic counselling and disease management. In addition, we tried to find a genotype-phenotype correlation in our patients. J. Trace Elem. Exp. Med. 12 :321-329, 1999. (C) 1999 Wiley-Liss, Inc.