The recent work by Vieira et al analyzes the best practice and key challenges of genetic counseling for Parkinson disease related to GBA1 variants (GBA1-PD). The paper has been authored by prominent experts in the field and serves as a useful guide for clinicians and researchers.
Variants in the GBA1 gene are an important risk factor for PD and Lewy body dementia, and a promising target for disease modification. Further, the phenotype of GBA1-PD is characterized by earlier onset, higher prevalence of non-motor symptoms, and faster progression, with a stratification of risk and phenotype dictated by the severity of different GBA1 variants.
Vieira et al discuss whether GBA1 genetic testing should be included in standard clinical care, noting that in recent years GBA1 sequencing has become increasingly available in some countries.
GBA1 testing is also essential for enrollment into clinical trials and offers important information for prognosis and family counseling.
Nonetheless, while genetic testing for PD is becoming increasingly more frequent, it is not readily available in most clinical settings and is mostly limited to neurology research centers. Testing is also complicated by technical limitations, as the GBA1 gene is notoriously difficult to sequence. As a result, some genotyping techniques only screen for the most common variants, leaving carriers of rarer and population-specific variants undetected.
The paper gives useful tips for discussing genetic results and presents important ethical considerations for GBA1 testing.
It stresses how counselling must be clear and balanced, should allow patients to make an informed decision about being tested, and should consider the psychological impact that testing could have for patients and asymptomatic family members.
Focus is given to the correct communication of the lifetime risk of PD, which needs to account for the background risk in the general population (estimated at about 3%) and the diverse risk linked to mild and severe GBA1 variants (fluctuating between 5% and 30%). Patients should also be invited to reflect on the implications of testing for family members, and whether they should share their results with their family. Moreover, the ramifications of genetic testing are diverse, not least those related to life and medical insurance coverage. Direct-to-customer genetic services pose a potential risk for patients, as results are often released without appropriate counseling. Stronger regulations and guidelines should be considered to mitigate these risks.
Vieira et al discuss the genetic diversity in different geographic areas, and the importance of involving under-represented populations in genetic testing. An exemplary case is that of the genetic landscape of PD in Africa, a continent where due to increased life expectancy, the incidence of PD is increasing rapidly, but where specific clinical and genetic features of PD have been poorly described. In this context, a recently discovered GBA1 intronic variant has been implicated in PD pathogenesis in African populations.
Ultimately, Vieira et al highlight the benefits of a wider use and understanding of GBA1 genetic testing but stress the importance of rigorous counselling and the need for structured guidelines.
Read the paper »