Lack of evidence for genetic association of saposins A, B, C and D with Parkinson's disease.,Brain

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Lack of evidence for genetic association of saposins A, B, C and D with Parkinson's disease.
Brain ( IF 14.5 ) Pub Date : 2020-08-13 , DOI: 10.1093/brain/awaa214
Yuri Ludwig Sosero _{1,

2} , Sara Bandres-Ciga ₃ , Sharon Hassin-Baer _{4,

5,

6,

7} , Roy N Alcalay _{8,

9} , Ziv Gan-Or _{1,

2,

10} ,

Affiliation

Department of Human Genetics, McGill University, Montréal, QC, H3A 1A1, Canada.
Montreal Neurological Institute, McGill University, Montréal, QC, H3A 1A1, Canada.
Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Department of Neurology, Sheba Medical Center, Tel Hashomer, 52621 Ramat-Gan, Israel.
Movement Disorders Institute, Sheba Medical Center, Tel Hashomer, 52621 Ramat Gan, Israel.
Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY 10032, USA.
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY 10032, USA.
Department of Neurology and Neurosurgery, McGill University, Montréal, QC, H3A 1A1, Canada.

We read with much interest the paper by Oji et al. (2020), which suggested an association between mutations in the saposin D region of PSAP and Parkinson’s disease. In their paper, the authors showed that variants in saposin D only partially segregate with Parkinson’s disease in three families of Japanese origin. For example, in Family 1, at least three carriers of the PSAP p.Q453P variant did not have Parkinson’s disease, including one of the parents who was an obligate carrier. The authors also report an association of six common intronic variants within the saposin D region of the gene when comparing Japanese Parkinson’s disease patients and East Asian control subjects. Among these six variants, rs4747203 and rs885828 remained significant also when comparing the combined Japanese-Taiwanese Parkinson’s disease cohorts with East Asian controls. These two variants are in perfect linkage disequilibrium (LD, r² = 1) in East Asians and represent the same allele. The authors further demonstrated, using different models, that PSAP mutations may affect prosaposin localization in the lysosome, autophagy, progressive motor decline in mice, and that patient-derived fibroblasts and dopaminergic neurons had α-synuclein accumulation.

更新日期：2020-09-20

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