Systematic Analysis and Insights Into the Mutation Spectrum and Ethnic Differences in ATP7B Mutations Associated With Wilson Disease

Background: ATP7B (ATPase copper transporting beta gene) is constituted of 21 exons, and codes for a 1465 amino acid. The protein of ATP7B plays an key role of copper metabolism. Many previous reports indicated that mutations in ATP7B are well known to cause defective copper transporting copper-transporting ATPase 2 protein leading to the accumulation of copper, resulting the Wilson disease.

Objectives: The meta-analysis was performed to comprehensive gain a thorough grasp of the spectrum of genetic variations.

Design: A meta-analysis was conducted according to the guiding of PRISMA. aiming to assess the diversity and frequency of mutations in the ATP7B gene, with an emphasis on mutations located within specific exons.

Data sources and methods: The dataset of detected mutations within their positions, types as well as nomenclature, were recorded from previous studies (spanning the year from 2013 to 2023). The analysis focused on exon-specific variations and their prevalence across different populations.

Results: A total of 40 studies were enrolled into current data analysis. Our comprehensive study revealed a variety of mutations, most notably over 50% of single nucleotide changes described, distributed over the 21 exons of the gene. Focusing on the exon 8, itisplayed the most diversity of mutations, with 18 studies identifying 53 unique variants, the majority of which were missense mutations (81.13%). Additionally, the variations c.2333G>A/T (p.R778Q/L), c.2305A>G (p.M769V), c.2336G>A (p.W779*), and c.2304dupC (p.M769HfsX26) are reported in many populations. The weighted mean of variants' proportion was used to calculate the pooled estimate of these percentages, which were 14.19% for c.2333G>A/T (p.R778Q/L), 2.70% for c.2305A>G (p.M769V), 1.42% for c.2336G>A (p.W779*), and 2.33% for c.2304dupC (p.M769HfsX26).

Conclusion: This design demonstrate to identify the spectrum of ATP7B gene's mutations, especially exon 8, offering important insights into the prevalence and significance of exon 8 mutations. Understanding the mutation in the ATP7B gene offers insights into the mechanisms behind WD and guides strategies for diagnosis and treatment.