Mutation Spectrum of Gene in Pediatric Patients with Wilson Disease in Vietnam

Background: Wilson disease (WD) is caused by mutations in the copper-transporting P-type adenosine triphosphatase encoded by the gene. In this study, we screened and identified the mutations among unrelated Vietnamese pediatric patients.

Methods: One-hundred-thirteen pediatric patients with clinically diagnosed WD were recruited. DNA samples were extracted from peripheral blood. Mutations in the gene were identified by Sanger sequencing.

Results: Approximately 98% of the clinically diagnosed WD patients carried mutations A total of 35 different variants were detected, including five novel mutations (L658P, L792P, T977K, IVS4 + 1G > A and IVS20 + 4A > G). Remarkably, this study revealed that S105* was the most prevalent variant (32.27%), followed by L1371P (9.09%), I1148T (7.27%), R778L (6.36%), T850I (5.45%), V176Sfs*28 and IVS14-2A > G (4.55%). Most mutations were located in the exon 2 (37.73%), exon 16 (10.00%), exon 8 (9.55%), exon 20 (9.09%), exon 10 and exon 18 (5.45%), exon 14 (5.00%), exon 13 and intron 14 (4.55%). We developed a streamlined procedure to quickly characterize mutations in the gene in the Vietnamese children, starting with sequencing exon 2 and subsequently to exons 8,10,13-16,18, and 20 to allow quick diagnosis of clinically suspected patients.

Conclusion: The mutational spectrum and hotspots of gene in the Vietnamese population were fairly different from other East Asian populations. A streamlined procedure was developed to screen exon 2 in gene among suspected WD patients to reduce genetically diagnostic cost, to facilitate early detection and intervention in countries with limited resources.