威尔逊病是一种由铜积累引起的复杂疾病,主要在肝脏和大脑。威尔逊病的遗传基础归因于ATP7B铜转运基因中致病变异的存在,防止铜通过胆道排泄。迄今为止,ATP7B仍然是唯一鉴定的与该疾病的发展有关的基因。我们对这种疾病的理解与鉴定特定的致病变体有关,这些变体在铜转运蛋白中表现出特定的损害。确定种族方面最常见的变体以促进其功能的测试至关重要。这项研究代表了ATP7B变体的初步综合分析,提供对广泛范围的致病突变的见解。这里,我们描述了迄今为止记录的1275种不同的ATP7B变体,特别强调他们的地区和种族流行。H1069Q错义变体是欧洲最常报道的,北美,北非,而R778L,C271*,而M645R变种在东亚最普遍,中东-南亚,和南美人口,分别。获得这些知识将有助于实施选择性突变筛选方法,针对特定种族或地理区域内确定的最主要的变异,以更好地诊断疾病。
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.