E Dagan1, I Schlesinger2, M Ayoub3, A Mory3, M Nassar4, A Kurolap3, J Peretz-Aharon2, R Gershoni-Baruch5. 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.
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.
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%) PDpatients 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 PDpatients carrying SMPD1 mutations were similar to those of PDpatients with no mutations in SMPD1, GBA and LRRK2 (n = 189). CONCLUSION: We maintain that disruptive mutations in SMPD1 constitute a risk factor for PD.
Authors: Roy N Alcalay; Victoria Mallett; Benoît Vanderperre; Omid Tavassoly; Yves Dauvilliers; Richard Y J Wu; Jennifer A Ruskey; Claire S Leblond; Amirthagowri Ambalavanan; Sandra B Laurent; Dan Spiegelman; Alexandre Dionne-Laporte; Christopher Liong; Oren A Levy; Stanley Fahn; Cheryl Waters; Sheng-Han Kuo; Wendy K Chung; Blair Ford; Karen S Marder; Un Jung Kang; Sharon Hassin-Baer; Lior Greenbaum; Jean-Francois Trempe; Pavlina Wolf; Petra Oliva; Xiaokui Kate Zhang; Lorraine N Clark; Melanie Langlois; Patrick A Dion; Edward A Fon; Nicolas Dupre; Guy A Rouleau; Ziv Gan-Or Journal: Mov Disord Date: 2019-02-20 Impact factor: 10.338
Authors: R N Alcalay; P Wolf; O A Levy; U J Kang; C Waters; S Fahn; B Ford; S H Kuo; N Vanegas; H Shah; C Liong; S Narayan; M W Pauciulo; W C Nichols; Z Gan-Or; G A Rouleau; W K Chung; P Oliva; J Keutzer; K Marder; X K Zhang Journal: Neurobiol Dis Date: 2018-02-02 Impact factor: 5.996
Authors: Tim E Moors; Jeroen J M Hoozemans; Angela Ingrassia; Tommaso Beccari; Lucilla Parnetti; Marie-Christine Chartier-Harlin; Wilma D J van de Berg Journal: Mol Neurodegener Date: 2017-01-25 Impact factor: 14.195