Abstract:
Background: Wilson’s disease is a rare, autosomal recessive genetic disorder that affects the biliary excretion of copper and its toxic accumulation in
various tissues, especially the liver and brain. It is widespread throughout the world, with a high prevalence in socio-culturally isolated communities.
The course of the disease and the age of onset depend on the site of mutation in the gene and the degree of functional impairment of the ATP7B protein.
The presence of the compound heterozygous patient complicates the comparative genetic and clinical evaluation. Therefore, it is necessary to analyze
Wilson’s variants in both the homozygous and the compound-heterozygous conditions to better understand the genotype-phenotype correlations and
the incomplete penetrance observed in this disorder. Outlining clear phenotype-genotype associations is difficult due to a large number of mutations
and different clinical presentations, but the involvement of epigenetic factors, modifying genes, environmental and lifestyle factors could explain the
differences in evolution and onset in members of the same family and not only.
Conclusions: Wilson’s disease is a genetically and clinically complex disorder. Although the results of genotype-phenotype correlation studies are not
well defined, and in some cases are completely contradictory, some peculiarities related to the age of onset, sex, clinical phenotype, and the evolution of
the disease have been highlighted. The interaction between genetic mutations and epigenetic factors may explain the phenotypic variability, but needs
further study.
