F-SSCP Screening for Two Common Mutations HIS1070GLN and GLY1267LYS in French Wilson Patients, and Report of Two Novel Mutations

Abstract

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism with an incidence of between 1:35 000 and 1:100 000 (1). The disorder manifests itself as chronic liver disease and/or later on, with neurological symptoms, due to gradual accumulation of copper (2,3). The gene responsible for Wilson disease has recently been mapped to chromosome 13 and cloned (4,5); it encodes a P-type ATPase involved in copper transport across membranes. To date more than 25 mutations have been identified in the ATP7B gene responsible for WD and among them two very common mutations have been reported. The first, His1070G ln, is a C to A transversion in exon 14 of the gene, with an allele frequency of 28% in the Northern European population. The other, Gly1267Lys, is a G to A transversion in exon 18 of the gene, with an allele frequency of 10% in the Northern European population (6). We investigated the prevalance of these 2 mutations in 40 French WD patients from 22 unrelated French families using fluorescence-based Single-Strand Conformational Polymorphisms (F-SSCP) analysis with subsequent direct sequencing of the abnormally shifted exons.