engleski

ATP7B gene mutations associated with incidence of Wilson disease in Croatian population

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism resulting from the absence or dysfunction of copper transporting P-type ATPase (ATP7B). More than 400 disease causing mutations of the ATP7B gene have been identified to date. Aim of ATP7B gene sequencing analysis is to confirm WD diagnosis in patients with atypical clinical presentation or equivocal copper studies and to investigate mutations present in croatian population. Genomic DNA was used to amplify 21 exons of the ATP7B gene. Sequencing analysis was performed by PCR and capillary electrophoresis with BigDye Terminator v3.1 kit on AB Genetic analyzer 3130xl. Here we report results of sequencing analysis of the ATP7B gene. We have analyzed coding region of the ATP7B gene of clinically diagnosed WD patients from Croatia, already screened for the most common His1069Gln mutation. It accounts for 54, 4% of Wilson disease alleles in croatian population. Out of the total number of 71 tested patients with WD, molecular analysis has confirmed the clinical diagnosis in 44 patients (61, 9%) so far. 17 (23, 9%) patients are homozygous for the most common His1069Gln mutation. In 13 patients (18, 4%) only one mutation has been identified. Mutations in croatian population are mostly distributed in exons 5, 8, 13, 14, 15, 18, 20 and 21 of the ATP7B gene. Sequencing analysis of the ATP7B gene is the best method to establish frequency of mutations in specific population so the screening test panel for most common mutations can be developed for this population.

ATP7B; Wilson disease; sequencing analysis; copper; mutation frequency

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