Wilson disease (WD) is an autosomal recessive disorder characterized by toxic accumulation of copper in the liver and subsequently in the brain and other organs. On the basis of sequence homology to known genes, the WD gene (ATP7B) appears to be a copper-transporting P-type ATPase. A search for ATP7B mutations in WD patients from five population samples, including 109 North American patients, revealed 27 distinct mutations, 18 of which are novel. A composite of published findings shows missense mutations in all exons-except in exons 1-5, which encode the six copper-binding motifs, and in exon 21, which spans the carboxy-terminus and the poly(A) tail. Over one-half of all WD mutations occur only rarely in any population sample. A splice-site mutation in exon 12 accounts for 3% of the WD mutations in our sample and produces an in-frame, 39-bp insertion in mRNA of patients homozygous, but not heterozygous, for the mutation. The most common WD mutation (His1069Glu) was represented in approximately 38% of all the WD chromosomes from the North American, Russian, and Swedish samples. In several population cohorts, this mutation deviated from Hardy-Weinberg equilibrium, with an overrepresentation of homozygotes. We did not find a significant correlation between His1069Glu homozygosity and several clinical indices, including age of onset, clinical manifestation, ceruloplasmin activity, hepatic copper levels, and the presence of Kayser-Fleischer rings. Finally, lymphoblast cell lines from individuals homozygous for His1069Glu and 4 other mutations all demonstrated significantly decreased copper-stimulated ATPase activity.

ABSTRACT. We investigated the effects of cadmium on lung cell DNA in immature mice. The mice were randomly divided into four groups: control group, low-dose group (1/100 LD 50 ), middle-dose group (1/50 LD 50 ), and high-dose group (1/25 LD 50 ); they were supplied with cadmium chloride or control water for 40 days. Lung cells collected from sacrificed mice were used to evaluate the extent of DNA damage by comet assay. The ratio of tailing cells, DNA tail length, DNA comet length, DNA tail moment, DNA olive tail moment, and percentage of DNA in the comet tail were measured. The rate of tailing lung cells exposed to cadmium increased significantly; the low-concentration group had significantly (P < 0.05) higher rates, and the middle-and high-concentration groups had higher (P < 0.01) rates compared to the control. DNA tail length, DNA comet length, DNA tail moment, and DNA olive tail moment all increased with the increase in cadmium doses, but compared with those of the control group, no significant differences in low-dose group were found (P > 0.05), and the differences in middleand high-dose groups were all highly significant (P < 0.01). The degree of DNA damage also increased with the increase of the cadmium concentrations. We conclude that cadmium significantly increases DNA ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (4): 4323-4329 (2012) X.F. Yang et al. 4324 damage in lung cells of immature mice in a dose-dependent manner.