Epidemiology of Wilson's Disease and Pathogenic Variants of the ATP7B Gene Leading to Diversified Protein Disfunctions

Abstract

Wilson's disease (WD) is an autosomal recessive disorder characterized by toxic accumulation of copper in the liver, brain, and other organs. The disease is caused by pathogenic variants in the ATP7B gene, which encodes a P-type copper transport ATPase. Diagnosing WD is associated with numerous difficulties due to the wide range of clinical manifestations and its unknown dependence on the physiological characteristics of the patient. This leads to a delay in the start of therapy and the subsequent deterioration of the patient's condition. However, in recent years, molecular genetic testing of patients using next generation sequencing (NGS) has been gaining popularity. This immediately affected the detection speed of WD. If, previously, the frequency of this disease was estimated at 1:35,000-45,000 people, now, when conducting large molecular genetic studies, the frequency is calculated as 1:7026 people. This certainly points to the problem of identifying WD patients. This review provides an update on the performance of epidemiological studies of WD and describes normal physiological functions of the protein and diversified disfunctions depending on pathogenic variants of the ATP7B gene. Future prospects in the development of WD genetic diagnostics are also discussed.

Keywords: Wilson’s disease (WD); copper transport ATPase; genetic diagnosis; prevalence.

Figure 1

Distribution of the most common pathogenic variants of the ATP7B gene in different regions of the world. The table lists the most common mutations and their percentage among all identified cases.

Figure 2

Structure and transmembrane organization of ATP7B.

Figure 3

Scheme of the ATP7B catalytic cycle.