Table 1 Pilot RbG study and recruitment of participants.

Project

The ProtectMove Research Unit project, focused on Parkinson’s disease and other neurological movement disorders, aims to investigate the genetic penetrance of specific variants of many genes, including the Parkin gene.

Pilot

In order to guarantee participants’ safety, the RbG was conceived as a pilot study focused on heterozygous Parkin variants that are pathogenic when inherited recessively in a homozygous or compound heterozygous state, but may influence symptoms dominantly, with very low penetrance, in a heterozygous state. Carriers of heterozygous Parkin variants may show subtle signs of Parkinson’s disease, slight abnormalities in the dopaminergic system [26, 27], morphometric changes in the basal ganglia [28], and compensatory changes in functional MRI studies [29]. The pilot study consisted of deeper neurological examinations, transcranial ultrasounds, and quantitative movements assessment to explore the genotype-phenotype relationships in heterozygous carriers versus non-carriers.

Design

The study was designed with a matched recruitment, where half of the invited participants carry the Parkin variant of interest in a heterozygous state, and the other half, who do not carry the variant, serve as controls. Controls were chosen as closely related to the carriers, with similar age and same sex, if possible.

Invitation

Participants were invited through the mail, which included a letter and information on the study.

Information provided in the invitation

The invitation explained the aim of the study, disclosed the disease and the variants under study, and the study’s design. Participants were informed that, according to current knowledge, heterozygosity of the Parkin variant under study does not cause Parkinson’s disease, but may cause an increase of the risk of prodromal neurological symptoms. As being a carrier of the variant in a heterozygotic state is not associated with any known clinical benefit, participants were informed that individual carrier status would not be disclosed.

Disclosure

Both researchers and participants did not know the participant’s individual carrier status (double blind).

Further communication

Invited participants were provided a phone number to call to ask clarifications and questions, if needed, and received a phone call from the study assistants to fix an appointment for the clinical examination and the empirical study.