Hi all! I was thinking about GBA1 and the heterogeneity we see regarding disease progression in PD. GBA1 pathogenic variants are typically classified as risk variants, mild, or severe. These categories really stem from the Gaucher’s disease literature.
The classification seems problematic to me since the severity of the mutation does not necessarily line up with the clinical severity in PD. Is anyone aware of efforts to “reclassify” GBA variants in PD, perhaps based on GCase levels or other biomarkers? I would be interested in hearing if others have thought about this conundrum and I would be interested in learning more about ongoing efforts to explain this. Thanks!
PS: Katja and Susen from our team are currently finalizing the MDSGene entry for GBA. GCase activity is (according to ACMG recommendation) for sure one of the hints but this is not available for all variants and depends on several factors, so it is variable among carriers. If you would like to discuss this in more detail, I can put you in touch with Katja and Susen.