Further delineation of the molecular pathology of Wilson disease in the Mediterranean population

Identification of a novel Wilson disease gene mutation frequent in Upper Austria: a genetic and clinical study

“…For example, in Apulia one third of WD patients carry the p.Gly591-Gly(c.1773C4G) mutation while most patients in Sardinia have mutations in the 5 0 -UTR region. 11,15,16 Both mutations are very rare Figure 2 Family tree of patients no. 13 and no.…”

“…[11][12][13] Most of the other mutations appear at low frequency and are associated with specific ethnic groups, or occur within single families. [14][15][16] Knowledge of the regional distribution of mutations of the WD gene is important to allow testing for the most common mutations in a population, thereby obtaining a rapid diagnosis in unclear cases, while comprehensive genetic testing will take at least several weeks currently. 17 In addition, the molecular analysis of ATP7B is important to facilitate the subsequent screening of family members.…”

Structure of human Wilson protein domains 5 and 6 and their interplay with domain 4 and the copper chaperone HAH1 in copper uptake

“…A different function for WLN5-6 with respect to the other metal-binding domains has been suggested, because WLN5-6 is found closest to the membrane and therefore may gate copper transfer to the intermembrane CIACPC site. The crucial role that WLN5 and WLN6 play in the function of WLNP are highlighted by two disease-causing missense mutations found in these domains, L492S and G591D (22), located in ␤ 1 of WLN5 and turn 2 of WLN6, respectively. In our structure of WLN5-6, Leu 492 (residue 8 of WLN5-6) extends into the hydrophobic core of the protein, and replacement with a hydrophilic residue would disrupt the hydrophobic interactions in the interior of WLN5, thus affecting the protein fold.…”

“…Human missense mutations found within metal-binding domains 1, 5, and 6 are known to give rise to Wilson disease (22), and these mutants show impaired interaction with HAH1 in a column-based assay (6). Mutational studies performed to address the role of the N-WLNP have found that, generally, the domains closest to the membrane seem to be the most important both for the ultimate incorporation of copper into Fet3 in yeast complementation assays and in the copper-dependent translocation of WLNP from the vesicular to the cytosolic membrane (23)(24)(25).…”

Molecular analysis of Wilson disease in Taiwan: identification of one novel mutation and evidence of haplotype-mutation association

“…Besides the 12 mutations previously reported by Tsai et al (1998), we identified another 4 missense mutations (A874V, V1216M, E1173K, and D1279G) in Taiwanese WND chromosomes; the A874V mutation was recently reported in Japanese and Korean WND chromosomes (Yamaguchi et al 1998;Kim et al 1998), and V1216M and E1173K were identified in Mediterranean WND chromosomes (Loudianos et al 1998(Loudianos et al , 1999. However, D1279G is a novel mutation with nonconservative amino acid substitution.…”