ATP7B Gene Variant Profile İdentified by NGS in Wilson's Disease

Area of Science:

• Genetics
• Biochemistry
• Medical Research

Background:

• Wilson disease (WD) is an autosomal recessive genetic disorder affecting copper metabolism.
• It is caused by mutations in the ATP7B gene, leading to copper accumulation in organs.
• Understanding the spectrum of ATP7B mutations is key to diagnosing and managing WD.

Purpose of the Study:

• To expand the known mutation profile of the ATP7B gene in Wilson disease patients.
• To investigate demographic and phenotypic variations associated with different ATP7B variants.
• To enhance the genotype-phenotype correlation for improved clinical management of WD.

Main Methods:

• Utilized next-generation sequencing for comprehensive ATP7B gene analysis.
• Evaluated clinical and demographic characteristics of patients diagnosed with WD.
• Correlated identified genetic variants with observed patient phenotypes.

Main Results:

• Identified eight likely pathogenic ATP7B variants (including D563N, Y532D, Y715Y, T977K, K1028*, E1086K, A1227Pfs*103, E1242K) associated with WD.
• Detected uniparental disomy in one patient case.
• Observed clinical heterogeneity linked to specific ATP7B variants, with T977K, A1003V, H1069Q, E1086K, and N1270S variants associated with hepatic failure.

Conclusions:

• The study broadens the spectrum of identified ATP7B variants in Wilson disease.
• Significant clinical heterogeneity exists among WD patients, influenced by specific ATP7B mutations.
• All symptomatic pediatric patients presented with hepatic involvement, underscoring the importance of early diagnosis.