Mutation analysis in patients of Mediterranean descent with Wilson disease: identification of 19 novel mutations

In this study, we report further results of mutation analysis of the ATP7B gene in Wilson disease (WD) patients of Mediterranean origin. A total of 13 6 WD chromosomes, 73 of which were of Italian, 43 of Turkish, 18 of Sardini an, and two of Spanish origin, were analysed and the mutation characterised in 84.5% of them. We found 50 different mutations of which 19 are novel, i ncluding three nonsense, one frameshift, and 15 missense mutations. The mut ations detected were rare and mostly found in the compound heterozygous sta te together with other mutations and only rarely in homozygosity. Most of t hese mutations lie in the transmembrane and ATP binding loop regions. These data expand our knowledge of both the structure-function relationships of the WD protein and the molecular pathology of WD, thus improving our capabi lity of prevention and genetic counselling.