Monica Gagliardi1, Grazia Annesi2, Radha Procopio3, Maurizio Morelli4, Grazia Iannello2, Giuseppe Bonapace5, Manuela Mancini4, Giuseppe Nicoletti2, Aldo Quattrone6. 1. Institute of Molecular Bioimaging and Physiology, National Research Council, Section of Germaneto, Catanzaro, Italy. Electronic address: monicg_2002@yahoo.it. 2. Institute of Molecular Bioimaging and Physiology, National Research Council, Section of Germaneto, Catanzaro, Italy. 3. Institute of Molecular Bioimaging and Physiology, National Research Council, Section of Germaneto, Catanzaro, Italy; Institute of Neurology, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy. 4. Institute of Neurology, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy. 5. Department of Medical and Surgical Science, Pediatrics Unit, University Magna Graecia, Catanzaro, Italy. 6. Institute of Molecular Bioimaging and Physiology, National Research Council, Section of Germaneto, Catanzaro, Italy; Neuroscience Research Center, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Italy.
Abstract
BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, and the most common neurodegenerative form of parkinsonism. Recently, a pathogenic mutation (p.N855S) in DNAJC13 was linked to autosomal dominant Lewy body PD in a Dutch-German-Russian Mennonite multi-incident kindred, and was found in five additional patients. In this study, we performed a comprehensive screening of the DNAJC13 gene in familial PD and sporadic PD to assess the frequency of known and novel rare nonsynonymous variants. METHODS: We screened 563 sporadic and 168 familial PD patients and a control series (n = 1000) for the coding region of DNAJC13. RESULTS: Our sequencing analysis identified two carriers of the c.2708G > A (p.R903K) variant in exon 24 of DNAJC13. One of these carriers is a familial PD. CONCLUSION: The p. R903K variant was not found in 1000 healthy controls and it is localized in a functional domain of the DNAJC13 protein. Further studies are necessary to evaluate the role of DNAJC13 variants in PD.
BACKGROUND:Parkinson's disease (PD) is the second most common neurodegenerative disorder, and the most common neurodegenerative form of parkinsonism. Recently, a pathogenic mutation (p.N855S) in DNAJC13 was linked to autosomal dominant Lewy body PD in a Dutch-German-Russian Mennonite multi-incident kindred, and was found in five additional patients. In this study, we performed a comprehensive screening of the DNAJC13 gene in familial PD and sporadic PD to assess the frequency of known and novel rare nonsynonymous variants. METHODS: We screened 563 sporadic and 168 familial PDpatients and a control series (n = 1000) for the coding region of DNAJC13. RESULTS: Our sequencing analysis identified two carriers of the c.2708G > A (p.R903K) variant in exon 24 of DNAJC13. One of these carriers is a familial PD. CONCLUSION: The p. R903K variant was not found in 1000 healthy controls and it is localized in a functional domain of the DNAJC13 protein. Further studies are necessary to evaluate the role of DNAJC13 variants in PD.
Authors: Prabhjyot Saini; Uladzislau Rudakou; Eric Yu; Jennifer A Ruskey; Farnaz Asayesh; Sandra B Laurent; Dan Spiegelman; Stanley Fahn; Cheryl Waters; Oury Monchi; Yves Dauvilliers; Nicolas Dupré; Lior Greenbaum; Sharon Hassin-Baer; Alberto J Espay; Guy A Rouleau; Roy N Alcalay; Edward A Fon; Ronald B Postuma; Ziv Gan-Or Journal: Neurobiol Aging Date: 2020-10-31 Impact factor: 4.673