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NTRK2 (TrkB gene) variants and temporal lobe epilepsy: A genetic association study
•The NTRK2 gene encodes a neurotrophic tyrosine kinase receptor family known as TrkB.•Polymorphisms of NTRK2 have been associated with neuropsychiatric disorders.•We studied NTRK2 variants in patients with temporal lobe epilepsy (TLE).•NTKR2 variants displayed association with epilepsy and some of e...
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| Published in: | Epilepsy research 2017-11, Vol.137, p.1-8 |
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| creator | Torres, Carolina Machado Siebert, Marina Bock, Hugo Mota, Suelen Mandelli Krammer, Bárbara Reis Duarte, Juliana Ávila Bragatti, José Augusto Castan, Juliana Unis de Castro, Luiza Amaral Saraiva-Pereira, Maria Luiza Bianchin, Marino Muxfeldt |
| description | •The NTRK2 gene encodes a neurotrophic tyrosine kinase receptor family known as TrkB.•Polymorphisms of NTRK2 have been associated with neuropsychiatric disorders.•We studied NTRK2 variants in patients with temporal lobe epilepsy (TLE).•NTKR2 variants displayed association with epilepsy and some of epilepsy characteristics.
The NTRK2 gene encodes a member of the neurotrophic tyrosine kinase receptor family known as TrkB. It is a membrane-associated receptor with signaling and cellular differentiation properties that has been involved in neuropsychiatric disorders, including epilepsy. We report here the frequencies of NTRK2 allele variants in patients with temporal lobe epilepsy (TLE) compared to controls without epilepsy and explore the impact of these polymorphisms on major clinical variables in TLE.
A case-control study comparing the frequencies of the NTRK2 gene polymorphisms beween 198 TLE Caucasian patients and 200 matching controls without epilepsy. In a second step, the impact of allelic variation on major clinical and electroencephalographic epilepsy variables was evaluated in the group of TLE patients. The following polymorphisms were determined by testing different regions of the NTRK2 gene: rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. To correct for multiple correlations the level of significance was set at p |
| doi_str_mv | 10.1016/j.eplepsyres.2017.08.010 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1936163830</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0920121117301304</els_id><sourcerecordid>1936163830</sourcerecordid><originalsourceid>FETCH-LOGICAL-c374t-48f987ce2731246e5f698d299602138f8609b184070eb14ad7bb1425b40614bf3</originalsourceid><addsrcrecordid>eNqFkE1P3DAQhi3Uil0-_gLykR6Szthex-kNUAuoCCS0nC3HmVTeZpPUzq60_56wS9sjp_fyzLwzD2McIUdA_XWV09DSkHaRUi4AixxMDghHbI6mEJk2Sn1icygFZCgQZ-wkpRUAFKDUMZsJY7SUAubs-XH5_FPwy2X8fc1_UUdf-NbF4LoxcdfVfKT10EfX8raviNMQ9rXf-NUeHoPnLqXeBzeGvuNp3NS7M_a5cW2i8_c8ZS8_vi9v7rKHp9v7m6uHzMtCjZkyTWkKT6KQKJSmRaNLU4uy1CBQmsZoKCs0arqZKlSuLqopxKJSoFFVjTxll4e9Q-z_bCiNdh2Sp7Z1HfWbZLGUGrU0EibUHFAf-5QiNXaIYe3iziLYN6N2Zf8btW9GLRg7GZ1GL95bNtWa6n-DfxVOwPUBoOnXbaBokw_UeapDJD_aug8ft7wCJwyKyg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1936163830</pqid></control><display><type>article</type><title>NTRK2 (TrkB gene) variants and temporal lobe epilepsy: A genetic association study</title><source>ScienceDirect Journals</source><creator>Torres, Carolina Machado ; Siebert, Marina ; Bock, Hugo ; Mota, Suelen Mandelli ; Krammer, Bárbara Reis ; Duarte, Juliana Ávila ; Bragatti, José Augusto ; Castan, Juliana Unis ; de Castro, Luiza Amaral ; Saraiva-Pereira, Maria Luiza ; Bianchin, Marino Muxfeldt</creator><creatorcontrib>Torres, Carolina Machado ; Siebert, Marina ; Bock, Hugo ; Mota, Suelen Mandelli ; Krammer, Bárbara Reis ; Duarte, Juliana Ávila ; Bragatti, José Augusto ; Castan, Juliana Unis ; de Castro, Luiza Amaral ; Saraiva-Pereira, Maria Luiza ; Bianchin, Marino Muxfeldt</creatorcontrib><description>•The NTRK2 gene encodes a neurotrophic tyrosine kinase receptor family known as TrkB.•Polymorphisms of NTRK2 have been associated with neuropsychiatric disorders.•We studied NTRK2 variants in patients with temporal lobe epilepsy (TLE).•NTKR2 variants displayed association with epilepsy and some of epilepsy characteristics.
The NTRK2 gene encodes a member of the neurotrophic tyrosine kinase receptor family known as TrkB. It is a membrane-associated receptor with signaling and cellular differentiation properties that has been involved in neuropsychiatric disorders, including epilepsy. We report here the frequencies of NTRK2 allele variants in patients with temporal lobe epilepsy (TLE) compared to controls without epilepsy and explore the impact of these polymorphisms on major clinical variables in TLE.
A case-control study comparing the frequencies of the NTRK2 gene polymorphisms beween 198 TLE Caucasian patients and 200 matching controls without epilepsy. In a second step, the impact of allelic variation on major clinical and electroencephalographic epilepsy variables was evaluated in the group of TLE patients. The following polymorphisms were determined by testing different regions of the NTRK2 gene: rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. To correct for multiple correlations the level of significance was set at p<0.01.
Patients with TLE showed a statistical trend for increase of the T/T genotype in rs10868235 compared to control (O.R.=1.90; 95%CI=1.17–3.09; p=0.01). Homozygous patients for the A allele in rs1443445 had earlier mean age at onset of seizures, p=0.009 (mean age of 16.6 versus 22.4years). We also observed that the T allele in rs3780645 was more frequent in patients who needed polytheraphy for seizure control than in patients on monotherapy, (O.R.=4.13; 95%CI=1.68–10.29; p=0.001). This finding may reflect an increased difficulty to obtain seizure control in this group of patients. No additional differences were observed in this study.
Patients with epilepsy showed a trend for a difference in rs10868235 allelic distribution compared to controls without epilepsy. NTRK2 variability influenced age at seizure onset and the pharmacological response to seizure control. As far as we know, this is the first study showing an association between NTKR2 allelic variants in human epilepsy. We believe that further studies in this venue will shade some light on the molecular mechanisms involved in epileptogenesis and in the clinical characteristics of epilepsy.</description><identifier>ISSN: 0920-1211</identifier><identifier>EISSN: 1872-6844</identifier><identifier>DOI: 10.1016/j.eplepsyres.2017.08.010</identifier><identifier>PMID: 28863320</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Age of Onset ; BDNF ; Brain - diagnostic imaging ; Brain - physiopathology ; Case-Control Studies ; Drug Resistant Epilepsy - genetics ; Drug Resistant Epilepsy - physiopathology ; Drug Resistant Epilepsy - therapy ; Electroencephalography ; Epilepsy, Temporal Lobe - genetics ; Epilepsy, Temporal Lobe - physiopathology ; Epilepsy, Temporal Lobe - therapy ; Epileptogenesis ; European Continental Ancestry Group - genetics ; Female ; Genetic Association Studies ; Genotyping Techniques ; Humans ; Male ; Membrane Glycoproteins - genetics ; Neuroimaging ; Neurotrophins ; Phenotype ; Polymorphism, Single Nucleotide ; Polymorphisms ; Receptor, trkB - genetics ; Temporal lobe epilepsy ; TrkB</subject><ispartof>Epilepsy research, 2017-11, Vol.137, p.1-8</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c374t-48f987ce2731246e5f698d299602138f8609b184070eb14ad7bb1425b40614bf3</citedby><cites>FETCH-LOGICAL-c374t-48f987ce2731246e5f698d299602138f8609b184070eb14ad7bb1425b40614bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28863320$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Torres, Carolina Machado</creatorcontrib><creatorcontrib>Siebert, Marina</creatorcontrib><creatorcontrib>Bock, Hugo</creatorcontrib><creatorcontrib>Mota, Suelen Mandelli</creatorcontrib><creatorcontrib>Krammer, Bárbara Reis</creatorcontrib><creatorcontrib>Duarte, Juliana Ávila</creatorcontrib><creatorcontrib>Bragatti, José Augusto</creatorcontrib><creatorcontrib>Castan, Juliana Unis</creatorcontrib><creatorcontrib>de Castro, Luiza Amaral</creatorcontrib><creatorcontrib>Saraiva-Pereira, Maria Luiza</creatorcontrib><creatorcontrib>Bianchin, Marino Muxfeldt</creatorcontrib><title>NTRK2 (TrkB gene) variants and temporal lobe epilepsy: A genetic association study</title><title>Epilepsy research</title><addtitle>Epilepsy Res</addtitle><description>•The NTRK2 gene encodes a neurotrophic tyrosine kinase receptor family known as TrkB.•Polymorphisms of NTRK2 have been associated with neuropsychiatric disorders.•We studied NTRK2 variants in patients with temporal lobe epilepsy (TLE).•NTKR2 variants displayed association with epilepsy and some of epilepsy characteristics.
The NTRK2 gene encodes a member of the neurotrophic tyrosine kinase receptor family known as TrkB. It is a membrane-associated receptor with signaling and cellular differentiation properties that has been involved in neuropsychiatric disorders, including epilepsy. We report here the frequencies of NTRK2 allele variants in patients with temporal lobe epilepsy (TLE) compared to controls without epilepsy and explore the impact of these polymorphisms on major clinical variables in TLE.
A case-control study comparing the frequencies of the NTRK2 gene polymorphisms beween 198 TLE Caucasian patients and 200 matching controls without epilepsy. In a second step, the impact of allelic variation on major clinical and electroencephalographic epilepsy variables was evaluated in the group of TLE patients. The following polymorphisms were determined by testing different regions of the NTRK2 gene: rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. To correct for multiple correlations the level of significance was set at p<0.01.
Patients with TLE showed a statistical trend for increase of the T/T genotype in rs10868235 compared to control (O.R.=1.90; 95%CI=1.17–3.09; p=0.01). Homozygous patients for the A allele in rs1443445 had earlier mean age at onset of seizures, p=0.009 (mean age of 16.6 versus 22.4years). We also observed that the T allele in rs3780645 was more frequent in patients who needed polytheraphy for seizure control than in patients on monotherapy, (O.R.=4.13; 95%CI=1.68–10.29; p=0.001). This finding may reflect an increased difficulty to obtain seizure control in this group of patients. No additional differences were observed in this study.
Patients with epilepsy showed a trend for a difference in rs10868235 allelic distribution compared to controls without epilepsy. NTRK2 variability influenced age at seizure onset and the pharmacological response to seizure control. As far as we know, this is the first study showing an association between NTKR2 allelic variants in human epilepsy. We believe that further studies in this venue will shade some light on the molecular mechanisms involved in epileptogenesis and in the clinical characteristics of epilepsy.</description><subject>Adult</subject><subject>Age of Onset</subject><subject>BDNF</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - physiopathology</subject><subject>Case-Control Studies</subject><subject>Drug Resistant Epilepsy - genetics</subject><subject>Drug Resistant Epilepsy - physiopathology</subject><subject>Drug Resistant Epilepsy - therapy</subject><subject>Electroencephalography</subject><subject>Epilepsy, Temporal Lobe - genetics</subject><subject>Epilepsy, Temporal Lobe - physiopathology</subject><subject>Epilepsy, Temporal Lobe - therapy</subject><subject>Epileptogenesis</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Female</subject><subject>Genetic Association Studies</subject><subject>Genotyping Techniques</subject><subject>Humans</subject><subject>Male</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Neuroimaging</subject><subject>Neurotrophins</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Polymorphisms</subject><subject>Receptor, trkB - genetics</subject><subject>Temporal lobe epilepsy</subject><subject>TrkB</subject><issn>0920-1211</issn><issn>1872-6844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqFkE1P3DAQhi3Uil0-_gLykR6Szthex-kNUAuoCCS0nC3HmVTeZpPUzq60_56wS9sjp_fyzLwzD2McIUdA_XWV09DSkHaRUi4AixxMDghHbI6mEJk2Sn1icygFZCgQZ-wkpRUAFKDUMZsJY7SUAubs-XH5_FPwy2X8fc1_UUdf-NbF4LoxcdfVfKT10EfX8raviNMQ9rXf-NUeHoPnLqXeBzeGvuNp3NS7M_a5cW2i8_c8ZS8_vi9v7rKHp9v7m6uHzMtCjZkyTWkKT6KQKJSmRaNLU4uy1CBQmsZoKCs0arqZKlSuLqopxKJSoFFVjTxll4e9Q-z_bCiNdh2Sp7Z1HfWbZLGUGrU0EibUHFAf-5QiNXaIYe3iziLYN6N2Zf8btW9GLRg7GZ1GL95bNtWa6n-DfxVOwPUBoOnXbaBokw_UeapDJD_aug8ft7wCJwyKyg</recordid><startdate>201711</startdate><enddate>201711</enddate><creator>Torres, Carolina Machado</creator><creator>Siebert, Marina</creator><creator>Bock, Hugo</creator><creator>Mota, Suelen Mandelli</creator><creator>Krammer, Bárbara Reis</creator><creator>Duarte, Juliana Ávila</creator><creator>Bragatti, José Augusto</creator><creator>Castan, Juliana Unis</creator><creator>de Castro, Luiza Amaral</creator><creator>Saraiva-Pereira, Maria Luiza</creator><creator>Bianchin, Marino Muxfeldt</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>201711</creationdate><title>NTRK2 (TrkB gene) variants and temporal lobe epilepsy: A genetic association study</title><author>Torres, Carolina Machado ; Siebert, Marina ; Bock, Hugo ; Mota, Suelen Mandelli ; Krammer, Bárbara Reis ; Duarte, Juliana Ávila ; Bragatti, José Augusto ; Castan, Juliana Unis ; de Castro, Luiza Amaral ; Saraiva-Pereira, Maria Luiza ; Bianchin, Marino Muxfeldt</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c374t-48f987ce2731246e5f698d299602138f8609b184070eb14ad7bb1425b40614bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Age of Onset</topic><topic>BDNF</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - physiopathology</topic><topic>Case-Control Studies</topic><topic>Drug Resistant Epilepsy - genetics</topic><topic>Drug Resistant Epilepsy - physiopathology</topic><topic>Drug Resistant Epilepsy - therapy</topic><topic>Electroencephalography</topic><topic>Epilepsy, Temporal Lobe - genetics</topic><topic>Epilepsy, Temporal Lobe - physiopathology</topic><topic>Epilepsy, Temporal Lobe - therapy</topic><topic>Epileptogenesis</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Female</topic><topic>Genetic Association Studies</topic><topic>Genotyping Techniques</topic><topic>Humans</topic><topic>Male</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Neuroimaging</topic><topic>Neurotrophins</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Polymorphisms</topic><topic>Receptor, trkB - genetics</topic><topic>Temporal lobe epilepsy</topic><topic>TrkB</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Torres, Carolina Machado</creatorcontrib><creatorcontrib>Siebert, Marina</creatorcontrib><creatorcontrib>Bock, Hugo</creatorcontrib><creatorcontrib>Mota, Suelen Mandelli</creatorcontrib><creatorcontrib>Krammer, Bárbara Reis</creatorcontrib><creatorcontrib>Duarte, Juliana Ávila</creatorcontrib><creatorcontrib>Bragatti, José Augusto</creatorcontrib><creatorcontrib>Castan, Juliana Unis</creatorcontrib><creatorcontrib>de Castro, Luiza Amaral</creatorcontrib><creatorcontrib>Saraiva-Pereira, Maria Luiza</creatorcontrib><creatorcontrib>Bianchin, Marino Muxfeldt</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Epilepsy research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Torres, Carolina Machado</au><au>Siebert, Marina</au><au>Bock, Hugo</au><au>Mota, Suelen Mandelli</au><au>Krammer, Bárbara Reis</au><au>Duarte, Juliana Ávila</au><au>Bragatti, José Augusto</au><au>Castan, Juliana Unis</au><au>de Castro, Luiza Amaral</au><au>Saraiva-Pereira, Maria Luiza</au><au>Bianchin, Marino Muxfeldt</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NTRK2 (TrkB gene) variants and temporal lobe epilepsy: A genetic association study</atitle><jtitle>Epilepsy research</jtitle><addtitle>Epilepsy Res</addtitle><date>2017-11</date><risdate>2017</risdate><volume>137</volume><spage>1</spage><epage>8</epage><pages>1-8</pages><issn>0920-1211</issn><eissn>1872-6844</eissn><abstract>•The NTRK2 gene encodes a neurotrophic tyrosine kinase receptor family known as TrkB.•Polymorphisms of NTRK2 have been associated with neuropsychiatric disorders.•We studied NTRK2 variants in patients with temporal lobe epilepsy (TLE).•NTKR2 variants displayed association with epilepsy and some of epilepsy characteristics.
The NTRK2 gene encodes a member of the neurotrophic tyrosine kinase receptor family known as TrkB. It is a membrane-associated receptor with signaling and cellular differentiation properties that has been involved in neuropsychiatric disorders, including epilepsy. We report here the frequencies of NTRK2 allele variants in patients with temporal lobe epilepsy (TLE) compared to controls without epilepsy and explore the impact of these polymorphisms on major clinical variables in TLE.
A case-control study comparing the frequencies of the NTRK2 gene polymorphisms beween 198 TLE Caucasian patients and 200 matching controls without epilepsy. In a second step, the impact of allelic variation on major clinical and electroencephalographic epilepsy variables was evaluated in the group of TLE patients. The following polymorphisms were determined by testing different regions of the NTRK2 gene: rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. To correct for multiple correlations the level of significance was set at p<0.01.
Patients with TLE showed a statistical trend for increase of the T/T genotype in rs10868235 compared to control (O.R.=1.90; 95%CI=1.17–3.09; p=0.01). Homozygous patients for the A allele in rs1443445 had earlier mean age at onset of seizures, p=0.009 (mean age of 16.6 versus 22.4years). We also observed that the T allele in rs3780645 was more frequent in patients who needed polytheraphy for seizure control than in patients on monotherapy, (O.R.=4.13; 95%CI=1.68–10.29; p=0.001). This finding may reflect an increased difficulty to obtain seizure control in this group of patients. No additional differences were observed in this study.
Patients with epilepsy showed a trend for a difference in rs10868235 allelic distribution compared to controls without epilepsy. NTRK2 variability influenced age at seizure onset and the pharmacological response to seizure control. As far as we know, this is the first study showing an association between NTKR2 allelic variants in human epilepsy. We believe that further studies in this venue will shade some light on the molecular mechanisms involved in epileptogenesis and in the clinical characteristics of epilepsy.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28863320</pmid><doi>10.1016/j.eplepsyres.2017.08.010</doi><tpages>8</tpages></addata></record> |
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| ispartof | Epilepsy research, 2017-11, Vol.137, p.1-8 |
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| source | ScienceDirect Journals |
| subjects | Adult Age of Onset BDNF Brain - diagnostic imaging Brain - physiopathology Case-Control Studies Drug Resistant Epilepsy - genetics Drug Resistant Epilepsy - physiopathology Drug Resistant Epilepsy - therapy Electroencephalography Epilepsy, Temporal Lobe - genetics Epilepsy, Temporal Lobe - physiopathology Epilepsy, Temporal Lobe - therapy Epileptogenesis European Continental Ancestry Group - genetics Female Genetic Association Studies Genotyping Techniques Humans Male Membrane Glycoproteins - genetics Neuroimaging Neurotrophins Phenotype Polymorphism, Single Nucleotide Polymorphisms Receptor, trkB - genetics Temporal lobe epilepsy TrkB |
| title | NTRK2 (TrkB gene) variants and temporal lobe epilepsy: A genetic association study |
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