The contribution of Niemann-Pick SMPD1 mutations to Parkinson disease in Ashkenazi Jews. Issue 9 (September 2015)

• Record Type: Journal Article
• Authors: Dagan, E.; Schlesinger, I.; Ayoub, M.; Mory, A.; Nassar, M.; Kurolap, A.; Peretz-Aharon, J.; Gershoni-Baruch, R.
• Is Part Of: Parkinsonism & related disorders. Volume 21:Issue 9(2015)
• Page Start: 1067
• Page End: 1071
• Publication Date: 2015-09
• Subjects: Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2015.06.016
• Languages: English
• ISSNs: 1353-8020

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Introduction</title> <p id="abspara0010">Parkinson disease is noted for its association with mutations in GBA and the p.G2019S mutation in <italic>LRRK2</italic>. This study aimed to evaluate the frequency of Ashkenazi founder mutations in sphingomyelin phosphodiesterase 1 (<italic>SMPD1</italic>) in Ashkenazi patients diagnosed with Parkinson's disease (PD); and their impact on PD phenotypic expression. <italic>SMPD1</italic> underlies the lysosomal storage disease - Niemann-Pick.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">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 <italic>SMPD1</italic> Ashkenazi mutations (c.996delC (fsP330), p.L302P and p.R496L) were investigated in patients and controls, previously evaluated for carriage of founder mutations in <italic>GBA</italic> and the p.G2019S mutation in <italic>LRRK2</italic>.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">Nine (3.1%) PD patients compared to two (0.5%) individuals from the control group were found to carry one of the three Ashkenazi <italic>SMPD1</italic> founder mutations (p = 0.007). The overall clinical characteristics of PD patients carrying <italic>SMPD1</italic> mutations were similar to those of PD patients with no mutations in <italic>SMPD1</italic>, <italic>GBA</italic> and <italic>LRRK2</italic> (n = 189).</p> </sec> <sec> <title id="sectitle0030">Conclusion</title> <p id="abspara0025">We maintain that disruptive mutations in <italic>SMPD1</italic> constitute a risk factor for PD.</p> </sec> </abstract>