title: The contribution of Niemann-Pick SMPD1 mutations to Parkinson disease in Ashkenazi Jews.
abstract: BACKGROUND
  Parkinson disease is noted for its association with mutations in GBA and the p.G2019S mutation in LRRK2. This study aimed to evaluate the frequency of Ashkenazi founder mutations in sphingomyelin phosphodiesterase 1 (SMPD1) in Ashkenazi patients diagnosed with Parkinson's disease (PD); and their impact on PD phenotypic expression. SMPD1 underlies the lysosomal storage disease - Niemann-Pick.
  
  
  METHODS
  A case (n = 287) control (n = 400) study was undertaken. All patients underwent a physical, neurobehavioral and neurologic examination that incorporated the Unified Parkinson's Disease Rating Scale. Three founder SMPD1 Ashkenazi mutations (c.996delC (fsP330), p.L302P and p.R496L) were investigated in patients and controls, previously evaluated for carriage of founder mutations in GBA and the p.G2019S mutation in LRRK2.
  
  
  RESULTS
  Nine (3.1%) PD patients compared to two (0.5%) individuals from the control group were found to carry one of the three Ashkenazi SMPD1 founder mutations (p = 0.007). The overall clinical characteristics of PD patients carrying SMPD1 mutations were similar to those of PD patients with no mutations in SMPD1, GBA and LRRK2 (n = 189).
  
  
  CONCLUSIONS
  We maintain that disruptive mutations in SMPD1 constitute a risk factor for PD.
authors.affiliation: Department of Nursing, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Dagan
authors.affiliation: Department of Neurology and the Cognitive Neurology Institute, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Schlesinger
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Ayoub
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Mory
authors.affiliation: The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Nassar
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Kurolap
authors.affiliation: Department of Neurology and the Cognitive Neurology Institute, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Peretz-Aharon
authors.affiliation: Department of Neurology and the Cognitive Neurology Institute, Rambam Health Care Campus, Haifa, Israel; Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel. Electronic address: rgershoni@rambam.health.gov.il.
authors.forename: R
authors.initials: R
authors.lastname: Gershoni-Baruch
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics; D006801:Humans; D007585:Jews / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012720:Severity of Illness Index; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; C543066:SMPD1 protein, human; D013108:Sphingomyelin Phosphodiesterase; D005962:Glucosylceramidase
keywords: GBA; Gaucher disease; LRRK2; Niemann-Pick disease; Parkinson's disease; SMPD1