Abstract:
Introduction. Wilson’s disease (WD) is a rare genetic disease with autosomal recessive transmission, thus screening of all
family members of newly diagnosed patients is recommended. Therefore, we aimed to analyze the proband’s family members to detect asymptomatic cases and early treatment initiation.
Material and methods. There were retrospectively evaluated 12 families, between 2008 - 2023. The Leipzig Scoring System was used to assess the diagnosis. Genetic testing was performed in all cases by the Sanger sequencing method, examining exons with a high and moderate frequency of mutations.
Results. All patients were of Caucasian origin, and originally from Moldova. No patient reported consanguineous relationships. In 9 families, first-degree relatives were tested - parents and siblings, in the other 3 cases only their descendants
were evaluated. In 6/12 cases: both parents were healthy carriers; in the other 3 families, one parent was a healthy carrier,
but the other parent had not been tested. Among siblings, 4 healthy carriers and 2 healthy siblings were identified. 7 new
family members with WD were identified in 5/12 families. 6 patients were asymptomatic, and 1 - was symptomatic. The
most frequent mutations detected were p.H1069Q and p.G1341D, both as compound heterozygous and homozygous recessive. A rare mutation has been detected.
Discussions. Genetic counseling is important for the family of the patient with Wilson’s disease, as the evaluation of
first-degree relatives is recommended by all international guidelines. First-degree relatives include the proband’s siblings,
as well as the proband’s offspring and parents. It is also important to assess distant relatives, especially in more isolated
areas. Although it is an autosomal recessive disorder, systemic family screening is recommended, as cases of paradoxical
transmission are recorded. The c.2292C>T variant, identified in one patient, represents a rare mutation that, when occurring in combination with another pathogenic mutation or a homozygous state, can cause WD.
Conclusions. Family screening greatly influences identifying asymptomatic members with Wilson’s disease. Genetic testing is very important in differentiating healthy carriers from asymptomatic members, especially when deciding treatment
tactics.
