The contribution of Niemann-Pick SMPD1 mutations to Parkinson disease in Ashkenazi Jews

E Dagan; I Schlesinger; M Ayoub; A Mory; M Nassar; A Kurolap; J Peretz-Aharon; R Gershoni-Baruch

doi:10.1016/j.parkreldis.2015.06.016

The contribution of Niemann-Pick SMPD1 mutations to Parkinson disease in Ashkenazi Jews

Parkinsonism Relat Disord. 2015 Sep;21(9):1067-71. doi: 10.1016/j.parkreldis.2015.06.016. Epub 2015 Jun 19.

Authors

E Dagan¹, I Schlesinger², M Ayoub³, A Mory³, M Nassar⁴, A Kurolap³, J Peretz-Aharon², R Gershoni-Baruch⁵

Affiliations

¹ Department of Nursing, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.
² 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.
³ Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel.
⁴ The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
⁵ 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.

PMID: 26169695
DOI: 10.1016/j.parkreldis.2015.06.016

Abstract

Introduction: 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).

Conclusion: We maintain that disruptive mutations in SMPD1 constitute a risk factor for PD.

Keywords: GBA; Gaucher disease; LRRK2; Niemann-Pick disease; Parkinson's disease; SMPD1.

MeSH terms

Aged
DNA Mutational Analysis
Female
Genetic Predisposition to Disease / genetics*
Glucosylceramidase / genetics
Humans
Jews / genetics
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Male
Middle Aged
Mutation / genetics*
Neuropsychological Tests
Parkinson Disease / ethnology
Parkinson Disease / genetics*
Protein Serine-Threonine Kinases / genetics
Severity of Illness Index
Sphingomyelin Phosphodiesterase / genetics*

Substances

LRRK2 protein, human
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Protein Serine-Threonine Kinases
SMPD1 protein, human
Sphingomyelin Phosphodiesterase
Glucosylceramidase