Reply: Saposin D variants are not a common cause of familial Parkinson ’s disease among Italians; and Lack of evidence for genetic association of saposins A, B, C and D with Parkinson’s disease

We reported three pathogenicPSAP mutations (c.1358A>C, p.Q453P; c.1431G>A, p.C451_L477del; and c.1235G>A, p.C412Y) for Japanese patients with autosomal dominant Parkinson ’s disease (Ojiet al., 2020). Three carriers of the p.Q453P variant in Family 1 did not have Parkinson ’s disease, which implicated thatPSAP variants that contributed to Parkinson ’s disease risk possibly have only a modest effect. We additionally performed whole-exome sequencing, which did not reveal any previously identified Parkinson’s disease-causing mutations (Ojiet al., 2020). Interestingly, the c.1431G>A variant (rs1409969130) is a rare variant that is only found in the South Asian gnomAD database. We also reported that rs885828, which is in perfect linkage disequilibrium with rs4747203, identified as significantly different in the Japanese cohort and the combined data of the Japanese and Taiwanese cohorts compared with the East Asian controls, but not in the Taiwanese single cohort. This could possibly be because of differences in the population and/or the average age at onset of Parkinson ’s disease in Japanese patients, which was significantly younger than Taiwanese patients (P  = 2.06  × 10−44, Welch ’st-test) (Ojiet al., 2020). Furthermore, rs885828 was not identified to be significantly different from Japanese controls from a previously published genome-wide association study, as discussed in our paper (Satakeet al., 2009;Ojiet al., 2020). Our case-control asso...
Source: Brain - Category: Neurology Source Type: research