Wilson Disease in a Turkish Population: Molecular Insights into an Old Disease with Reported and Novel Variants

Objective: Wilson's disease (WD) is a rare autosomal recessive genetic liver disorder with hepatic, neurological, or psychiatric manifestations between 1 st to 5 th decades.WD is caused by homozygous or compound heterozygous pathogenic variants in the ATP7B gene.In this study, we aimed to contribute to the ATP7B gene variant spectrum in a Turkish population of WD patients. Methods:We investigated 49 patients from 46 families to determine the underlying molecular etiology of WD.DNA samples were extracted from peripheral blood.The molecular genetic diagnosis was performed using the next-generation sequencing method.Results: Molecular genetic analysis revealed 26 different variants, two of which were novel c.1707+4A>G (IVS4+4A>G) and p.M497K in 34 patients from 31 different families.p.M769Hfs*26 was the variant with the highest allele frequency at 11.3%, followed by the p.H1069Q variant (8%).The classification of the variants according to the molecular mechanism was as follows: missense 61.5%, splice site and frameshift 15.4%, and non-sense 0.08%. Conclusion:In this study, we aimed to contribute the variant spectrum of the ATP7B gene in the Turkish population and the genetic profile of WD with the obtained data.