The mutation spectrum and ethnic distribution of Wilson disease, a review

Wilson's disease is a complicated medical condition caused by the accumulation of copper, mostly in the liver and brain. The genetic basis of Wilson's disease is attributed to the presence of pathogenic variants in the ATP7B copper-transporting gene, which prevents the excretion of copper through the biliary tract. To date, ATP7B remains the only identified gene that has been linked to the development of this disease. Our understanding of the disease has been associated with the identification of particular disease-causing variants that present specific impairments in copper transporters. It is crucial to identify the most frequent variant in terms of ethnicity to facilitate testing of its functionality. This study represents the initial comprehensive analysis of ATP7B variants, providing insights into the extensive range of disease-causing mutations. Here, we describe the 1275 distinct ATP7B variants documented so far, with particular emphasis on their regional and ethnic prevalence. The H1069Q missense variant is the most frequently reported in Europe, Northern America, and North Africa, whereas the R778L, C271*, and M645R variants are the most prevalent in the East Asian, Middle Eastern-South Asian, and South American populations, respectively. Acquiring such knowledge would facilitate the implementation of a selective mutation screening approach, targeting the most predominant variant identified within a specific ethnic group or geographic region for better diagnosis of the disease.