Preimplantation Genetic Testing (PGT) to Reduce the Risk for GBA-Related Parkinson's Disease: Expanding the...

Preimplantation genetic testing (PGT) is practiced worldwide, allowing the prevention of the transmission and expression of various genetic conditions. Socio-ethical considerations of justified applications for PGT are part of an ongoing debate. Pathogenic variants in the glucocerebrosidase (GBA1) gene, causing Gaucher disease (GD), have emerged as a risk factor for Parkinson's disease (PD) in both patients and carriers. Genotype-phenotype correlations exist between different GBA1 pathogenic variants and the risk to develop PD: mild pathogenic variants increase the risk of developing PD by ~3-fold, while severe pathogenic variants increase this risk by ~15-fold, occurring at a younger age. A woman with GD, a compound heterozygote of N370S (now commonly described as c.1226A>G (N409S)-mild pathogenic variant) and 84insG (severe pathogenic variant), had PGT consulting before planned in vitro-fertilization. Her mother, an 84insG carrier, had early-onset PD. GBA1 sequencing of her spouse was negative. We discussed the selection for N370S carrier embryos to reduce PD risk. This case report demonstrates the expansion of PGT for late-onset conditions. These novel indications will increase the number of subjects who would be candidates for PGT. The medical and bioethical considerations of these cases should be acknowledged by the professional community and discussed with couples during genetic counseling.