Saposin D variants are not a common cause of familial Parkinson ’s disease among Italians

We read with great interest the work byOjiet al. (2020) entitled ‘Variants in saposin D domain of prosaposin gene linked to Parkinson’s disease’, as we were also undertaking a genetic screening of the saposin D domain of prosaposin gene (PSAP). Saposins act as cofactors for different lysosomal hydroxylases, promoting their catalytic activity (Kishimotoet al., 1992). To date, it is widely accepted that the lysosomal pathway plays a pivotal role in neuron homeostasis and, in turn, that its impairment is a major pathogenic event in neurodegenerative diseases, including Parkinson ’s disease (Dehayet al., 2013).PSAP codes for four saposins (A, B, C and D), which are derived from a common precursor by proteolytic cleavage (Kishimotoet al., 1992). Mutations in both saposin C and D have been reported to cause Gaucher disease (Diaz-Fontet al., 2005;Tylki-Szymanskaet al., 2007). Concerning Parkinson ’s disease, while the role of variants in saposin C was previously explored without finding a statistically significant association (Ouled Amar Bencheikhet al., 2018), saposin D has long been neglected.Ojiet al. (2020) describe three novel pathogenic mutations in the saposin D domain of thePSAP gene causing autosomal dominant Parkinson ’s disease and found an association between two other intronicPSAP gene variants (rs4747203 and rs885828) and sporadic Parkinson ’s disease in a combined Japanese and Taiwanese cohort.
Source: Brain - Category: Neurology Source Type: research