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

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

E Dagan  1 , I Schlesinger  2 , M Ayoub  3 , A Mory  3 , M Nassar  4 , A Kurolap  3 , J Peretz-Aharon  2 , R Gershoni-Baruch  5
Affiliations

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

E Dagan et al. Parkinsonism Relat Disord. 2015 Sep.

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.

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Comment in

  • SMPD1 mutations and Parkinson disease.
    Dagan E, Adir V, Schlesinger I, Borochowitz Z, Ayoub M, Mory A, Nassar M, Kurolap A, Aharon-Peretz J, Gershoni-Baruch R. Dagan E, et al. Parkinsonism Relat Disord. 2015 Oct;21(10):1296-7. doi: 10.1016/j.parkreldis.2015.08.019. Epub 2015 Aug 20. Parkinsonism Relat Disord. 2015. PMID: 26318962 No abstract available.
  • The emerging role of SMPD1 mutations in Parkinson's disease: Implications for future studies.
    Gan-Or Z, Orr-Urtreger A, Alcalay RN, Bressman S, Giladi N, Rouleau GA. Gan-Or Z, et al. Parkinsonism Relat Disord. 2015 Oct;21(10):1294-5. doi: 10.1016/j.parkreldis.2015.08.018. Epub 2015 Aug 20. Parkinsonism Relat Disord. 2015. PMID: 26320887

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