Twenty-Four Novel Mutations in Wilson Disease Patients of Predominantly Italian Origin

Abstract

Herein we report the results of mutation analysis of the ATP7B gene in a group of 134 Wilson disease (WD) families (268 chromosomes) prevalently of Italian origin. Using the SSCP and sequencing methods we identified 71 disease-causing mutations. Twenty-four were novel, while 19 more mutations already described, were identified in new populations in this study. A known mutation G591D showed a regional distribution, since it was only detected in 38.5% of the analyzed chromosomes in WD patients originating from Apulia, a region of South Italy. Detection of new mutations in the ATP7B gene increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD.

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

“…24 In the Island of Gran Canaria, an archipelago near the northwest Atlantic coast of Africa, a high frequency of the very rare p.Leu708Pro(c.2123T4C) mutation was described, finding a total of 12 homozygous and 7 heterozygous individuals. 13 All known WD patients in Iceland carry the Y760X (c.2007_2013del, exon 7) mutation.…”

Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease

“…DNA samples not completely characterized by the first step of analysis or those found to have a new missense mutation were further analyzed for the remaining exons of the ATP7B gene by single-strand conformational polymorphism and sequencing analysis. 17 Statistical Analysis Continuous variables (ceruloplasmin, urinary copper, and liver copper) were presented as numbers of patients, means, medians, and standard deviations, whereas discrete variables (clinical manifestations at presentation and the presence or absence of KF rings) were presented as percentages. Normally distributed continuous variables were presented as means and standard deviations and were compared between groups by analysis of variance with post hoc testing (Scheffe's test).…”

Genotype–phenotype correlation in Italian children with Wilson’s disease

“…Patients were analyzed for 12 exons [5,6,8,10,[12][13][14][15][16][17][18][19], where most mutations reside on the basis of our previous studies using SSCP and sequencing methods. DNA samples not completely characterized by the first step of analysis or those found to have a new missense mutation, were further analyzed for the remaining exons of the ATP7B gene, by SSCP and sequencing analysis [17].…”