A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease
Background The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2‐PD and more severe among patients with GBA‐PD; however, whether an additive phenotypical effect occurs among dual‐mutation carriers requires validation. Objective The objective of this study was to explore...
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| Veröffentlicht in: | Movement disorders 2020-07, Vol.35 (7), p.1249-1253 |
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| creator | Omer, Nurit Giladi, Nir Gurevich, Tanya Bar‐Shira, Anat Gana‐Weisz, Mali Goldstein, Orly Kestenbaum, Meir Cedarbaum, Jesse M. Orr‐Urtreger, Avi Mirelman, Anat Thaler, Avner |
| description | Background
The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2‐PD and more severe among patients with GBA‐PD; however, whether an additive phenotypical effect occurs among dual‐mutation carriers requires validation.
Objective
The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single‐mutation presentation.
Methods
Patients with PD were genotyped for the G2019S‐LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA‐PD, severe GBA‐PD, LRRK2‐PD, and LRRK2+GBA‐PD. Clinical symptoms were evaluated using performance‐based measures.
Results
A total of 1090 patients with idiopathic PD, 155 patients with LRRK2‐PD, 155 patients with mild GBA‐PD, 56 patients with severe GBA‐PD, and 27 patients with LRRK2+GBA‐PD participated in this study. The patients with LRRK2‐PD and LRRK2+GBA‐PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P |
| doi_str_mv | 10.1002/mds.28066 |
| format | Article |
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The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2‐PD and more severe among patients with GBA‐PD; however, whether an additive phenotypical effect occurs among dual‐mutation carriers requires validation.
Objective
The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single‐mutation presentation.
Methods
Patients with PD were genotyped for the G2019S‐LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA‐PD, severe GBA‐PD, LRRK2‐PD, and LRRK2+GBA‐PD. Clinical symptoms were evaluated using performance‐based measures.
Results
A total of 1090 patients with idiopathic PD, 155 patients with LRRK2‐PD, 155 patients with mild GBA‐PD, 56 patients with severe GBA‐PD, and 27 patients with LRRK2+GBA‐PD participated in this study. The patients with LRRK2‐PD and LRRK2+GBA‐PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P < 0.01) and better olfaction (P < 0.01) compared with GBA‐PD.
Conclusions
Patients with LRRK2+GBA‐PD were symptomatically similar to patients with LRRK2‐PD, suggesting a dominant effect of LRRK2 over GBA in the phenotypic presentation. © 2020 International Parkinson and Movement Disorder Society</description><identifier>ISSN: 0885-3185</identifier><identifier>EISSN: 1531-8257</identifier><identifier>DOI: 10.1002/mds.28066</identifier><identifier>PMID: 32353202</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>GBA ; Genotype ; Glucosylceramidase ; Glucosylceramidase - genetics ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics ; LRRK2 ; LRRK2 protein ; Movement disorders ; Mutation ; Mutation - genetics ; Neurodegenerative diseases ; Olfaction ; Parkinson Disease - genetics ; Parkinson's disease ; Phenotypes</subject><ispartof>Movement disorders, 2020-07, Vol.35 (7), p.1249-1253</ispartof><rights>2020 International Parkinson and Movement Disorder Society</rights><rights>2020 International Parkinson and Movement Disorder Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3536-c9e86967e1b177edced9dde3a470fe3e267739be9e4da279e3eaaa39f42df7853</citedby><cites>FETCH-LOGICAL-c3536-c9e86967e1b177edced9dde3a470fe3e267739be9e4da279e3eaaa39f42df7853</cites><orcidid>0000-0001-7629-8120</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmds.28066$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmds.28066$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32353202$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Omer, Nurit</creatorcontrib><creatorcontrib>Giladi, Nir</creatorcontrib><creatorcontrib>Gurevich, Tanya</creatorcontrib><creatorcontrib>Bar‐Shira, Anat</creatorcontrib><creatorcontrib>Gana‐Weisz, Mali</creatorcontrib><creatorcontrib>Goldstein, Orly</creatorcontrib><creatorcontrib>Kestenbaum, Meir</creatorcontrib><creatorcontrib>Cedarbaum, Jesse M.</creatorcontrib><creatorcontrib>Orr‐Urtreger, Avi</creatorcontrib><creatorcontrib>Mirelman, Anat</creatorcontrib><creatorcontrib>Thaler, Avner</creatorcontrib><title>A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease</title><title>Movement disorders</title><addtitle>Mov Disord</addtitle><description>Background
The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2‐PD and more severe among patients with GBA‐PD; however, whether an additive phenotypical effect occurs among dual‐mutation carriers requires validation.
Objective
The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single‐mutation presentation.
Methods
Patients with PD were genotyped for the G2019S‐LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA‐PD, severe GBA‐PD, LRRK2‐PD, and LRRK2+GBA‐PD. Clinical symptoms were evaluated using performance‐based measures.
Results
A total of 1090 patients with idiopathic PD, 155 patients with LRRK2‐PD, 155 patients with mild GBA‐PD, 56 patients with severe GBA‐PD, and 27 patients with LRRK2+GBA‐PD participated in this study. The patients with LRRK2‐PD and LRRK2+GBA‐PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P < 0.01) and better olfaction (P < 0.01) compared with GBA‐PD.
Conclusions
Patients with LRRK2+GBA‐PD were symptomatically similar to patients with LRRK2‐PD, suggesting a dominant effect of LRRK2 over GBA in the phenotypic presentation. © 2020 International Parkinson and Movement Disorder Society</description><subject>GBA</subject><subject>Genotype</subject><subject>Glucosylceramidase</subject><subject>Glucosylceramidase - genetics</subject><subject>Humans</subject><subject>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics</subject><subject>LRRK2</subject><subject>LRRK2 protein</subject><subject>Movement disorders</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Neurodegenerative diseases</subject><subject>Olfaction</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson's disease</subject><subject>Phenotypes</subject><issn>0885-3185</issn><issn>1531-8257</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtLAzEURoMoWh8L_4AEXKiL0TyaZLKsryq2KD7WIZ3caHQ6o5MZpP_e2FYXgqsLH4fD5SC0S8kxJYSdTF08ZjmRcgX1qOA0y5lQq6hH8lxknOZiA23G-EoIpYLKdbTBGRecEdZDZoDv6hjDpAQ8rl3ws1A94wvvoWhx7XH7AnjICNUPeNy1tg11hUM1n0f39zcMD6ECnMbhaTLZ5i1Usa4OIj4PEWyEbbTmbRlhZ3m30NPlxePZVTa6HV6fDUZZkT6RWaEhl1oqoBOqFLgCnHYOuO0r4oEDk0pxPQENfWeZ0mmy1nLt-8x5lQu-hQ4X3vem_uggtmYaYgFlaSuou2gY10pKxRlL6P4f9LXumip9Z1ifCSEVFd_U0YIqmtSnAW_emzC1zcxQYr6rm1TdzKsndm9p7CZTcL_kT-YEnCyAz1DC7H-TGZ8_LJRf466IoA</recordid><startdate>202007</startdate><enddate>202007</enddate><creator>Omer, Nurit</creator><creator>Giladi, Nir</creator><creator>Gurevich, Tanya</creator><creator>Bar‐Shira, Anat</creator><creator>Gana‐Weisz, Mali</creator><creator>Goldstein, Orly</creator><creator>Kestenbaum, Meir</creator><creator>Cedarbaum, Jesse M.</creator><creator>Orr‐Urtreger, Avi</creator><creator>Mirelman, Anat</creator><creator>Thaler, Avner</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7629-8120</orcidid></search><sort><creationdate>202007</creationdate><title>A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease</title><author>Omer, Nurit ; Giladi, Nir ; Gurevich, Tanya ; Bar‐Shira, Anat ; Gana‐Weisz, Mali ; Goldstein, Orly ; Kestenbaum, Meir ; Cedarbaum, Jesse M. ; Orr‐Urtreger, Avi ; Mirelman, Anat ; Thaler, Avner</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3536-c9e86967e1b177edced9dde3a470fe3e267739be9e4da279e3eaaa39f42df7853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>GBA</topic><topic>Genotype</topic><topic>Glucosylceramidase</topic><topic>Glucosylceramidase - genetics</topic><topic>Humans</topic><topic>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics</topic><topic>LRRK2</topic><topic>LRRK2 protein</topic><topic>Movement disorders</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Neurodegenerative diseases</topic><topic>Olfaction</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson's disease</topic><topic>Phenotypes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Omer, Nurit</creatorcontrib><creatorcontrib>Giladi, Nir</creatorcontrib><creatorcontrib>Gurevich, Tanya</creatorcontrib><creatorcontrib>Bar‐Shira, Anat</creatorcontrib><creatorcontrib>Gana‐Weisz, Mali</creatorcontrib><creatorcontrib>Goldstein, Orly</creatorcontrib><creatorcontrib>Kestenbaum, Meir</creatorcontrib><creatorcontrib>Cedarbaum, Jesse M.</creatorcontrib><creatorcontrib>Orr‐Urtreger, Avi</creatorcontrib><creatorcontrib>Mirelman, Anat</creatorcontrib><creatorcontrib>Thaler, Avner</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Movement disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Omer, Nurit</au><au>Giladi, Nir</au><au>Gurevich, Tanya</au><au>Bar‐Shira, Anat</au><au>Gana‐Weisz, Mali</au><au>Goldstein, Orly</au><au>Kestenbaum, Meir</au><au>Cedarbaum, Jesse M.</au><au>Orr‐Urtreger, Avi</au><au>Mirelman, Anat</au><au>Thaler, Avner</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease</atitle><jtitle>Movement disorders</jtitle><addtitle>Mov Disord</addtitle><date>2020-07</date><risdate>2020</risdate><volume>35</volume><issue>7</issue><spage>1249</spage><epage>1253</epage><pages>1249-1253</pages><issn>0885-3185</issn><eissn>1531-8257</eissn><abstract>Background
The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2‐PD and more severe among patients with GBA‐PD; however, whether an additive phenotypical effect occurs among dual‐mutation carriers requires validation.
Objective
The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single‐mutation presentation.
Methods
Patients with PD were genotyped for the G2019S‐LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA‐PD, severe GBA‐PD, LRRK2‐PD, and LRRK2+GBA‐PD. Clinical symptoms were evaluated using performance‐based measures.
Results
A total of 1090 patients with idiopathic PD, 155 patients with LRRK2‐PD, 155 patients with mild GBA‐PD, 56 patients with severe GBA‐PD, and 27 patients with LRRK2+GBA‐PD participated in this study. The patients with LRRK2‐PD and LRRK2+GBA‐PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P < 0.01) and better olfaction (P < 0.01) compared with GBA‐PD.
Conclusions
Patients with LRRK2+GBA‐PD were symptomatically similar to patients with LRRK2‐PD, suggesting a dominant effect of LRRK2 over GBA in the phenotypic presentation. © 2020 International Parkinson and Movement Disorder Society</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>32353202</pmid><doi>10.1002/mds.28066</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-7629-8120</orcidid></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | GBA Genotype Glucosylceramidase Glucosylceramidase - genetics Humans Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics LRRK2 LRRK2 protein Movement disorders Mutation Mutation - genetics Neurodegenerative diseases Olfaction Parkinson Disease - genetics Parkinson's disease Phenotypes |
| title | A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease |
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