Researchers from China identified 14 new suspected pathogenic variants in the ATP7B gene in 12 patients with clinically suspected Wilson disease, according to a study.

This finding may increase the diagnostic accuracy of the disease and ensure that patients with the clinically suspected disease receive the right treatment in a timely manner, the researcher noted.

The diagnosis of Wilson disease remains challenging, with some patients with clinically suspected disease not having any detectable pathogenic ATP7B variants, the authors noted.

Read more about the diagnosis of Wilson disease

Here, a team of researchers led by Zhi-Ying Wu, from the Zhejiang University School of Medicine in Hangzhou, China, analyzed such patients from their center. The study is published in The Journal of Molecular Diagnostics.

The researchers screened the full-length sequence of the ATP7B gene using next-generation sequencing. They then analyzed the synonymous and intronic variants to determine their pathogenicity.

Among the 14 pathogenic variants that the researchers identified, there were 9 synonymous variants and 5 intronic variants. Of the synonymous variants, 4 led to splicing changes in the ATP7B gene. The same was also the case for 4 intronic variants. 

Based on these new findings, the researchers were able to molecularly diagnose Wilson disease in 8 patients who were clinically suspected of having the disease. All 8 patients had a late age of onset of the disease.

Wilson disease is a rare genetic disease affecting copper metabolism. It is caused by mutations in the ATP7B gene, which encodes ATPase 2, a protein responsible for transporting copper from the liver to other regions in the body. When the function of ATPase 2 is impaired, excess copper accumulates inside the liver, causing damage and resulting in symptoms such as steatosis, hepatitis, liver fibrosis, and acute liver failure.


Xu WQ, Wang RM, Dong Y, Wu ZY. Pathogenicity of intronic and synonymous variants of ATP7B in Wilson disease. J Mol Diagn. Published online November 4, 2022. doi:10.1016/j.jmoldx.2022.10.002