Association of NOTCH2NLC Repeat Expansions With Parkinson Disease
IMPORTANCE: The presence of Notch homolog 2 N-terminal-like C (NOTCH2NLC) repeat expansions are associated with neuronal intranuclear inclusion body disease (NIID), with varied neurological signs, including neuropathy, ataxia, parkinsonism, and tremor. To date, genetic screening of NOTCH2NLC GGC rep...
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| Veröffentlicht in: | Archives of neurology (Chicago) 2020-12, Vol.77 (12), p.1559-1563 |
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| creator | Ma, Dongrui Tan, Yi Jayne Ng, Adeline S. L Ong, Helen L Sim, Weiying Lim, Weng Khong Teo, Jing Xian Ng, Ebonne Y. L Lim, Ee-Chien Lim, Ee-Wei Chan, Ling-Ling Tan, Louis C. S Yi, Zhao Tan, Eng-King |
| description | IMPORTANCE: The presence of Notch homolog 2 N-terminal-like C (NOTCH2NLC) repeat expansions are associated with neuronal intranuclear inclusion body disease (NIID), with varied neurological signs, including neuropathy, ataxia, parkinsonism, and tremor. To date, genetic screening of NOTCH2NLC GGC repeats in a cohort with typical Parkinson disease (PD) appears not to have been reported. OBJECTIVE: To investigate if NOTCH2NLC GGC expansions are present in a cohort of patients with PD and controls. DESIGN, SETTING, AND PARTICIPANTS: This case-control study was conducted in 2 tertiary movement disorder centers in Singapore. Participants were recruited and followed up from January 2005 to January 2020. The presence of NOTCH2NLC GGC expansion repeats was screened using polymerase chain reaction tests, and representative samples were verified with long-read genome sequencing. MAIN OUTCOMES AND MEASURES: Qualitative and quantitative comparisons between participants with sporadic PD, healthy control participants, and individuals with NIID. RESULTS: A total of 2076 participants, including 1000 with sporadic PD (600 men [60.0%]; mean age at onset, 62.6 [7.7] years) and 1076 healthy controls (581 men [54.0%]; mean age at study recruitment, 54.9 [9.4] years) were recruited. A total of 13 patients with PD and no healthy control participants were identified as carrying NOTCH2NLC GGC repeat expansions of more than 40 units; the frequency of more than 40 repeat expansions was higher in participants with PD than controls (P |
| doi_str_mv | 10.1001/jamaneurol.2020.3023 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7445625</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><ama_id>2769859</ama_id><sourcerecordid>2475526121</sourcerecordid><originalsourceid>FETCH-LOGICAL-a455t-a16bc93ec291d6edfdb681870ff82376466feb65b3d0984c1dc4652f12477dfc3</originalsourceid><addsrcrecordid>eNpdkUtrGzEUhUVIiI3rPxBCGcimG7t6S7MpGOfRgnFCSOlSaDRSLHc8cqSZ0v77ythxm2gjwfnO5R4dAC4RnCII0ee13ujW9jE0UwwxnBKIyQkYYsTlhCMmTo9vWg7AOKU1zEdCSAk9BwOCJcOM0CGYzVIKxuvOh7YIrljeP82_4uViXjzardVdcfN7q9uU1VT88N2qeNDxp29Tpq99sjrZD-DM6SbZ8eEege-3N3nIZHF_920-W0w0ZaybaMQrUxJrcIlqbmtXV1wiKaBzEhPBKefOVpxVpIalpAbVhnKGHcJUiNoZMgJf9nO3fbWxtbFtF3WjttFvdPyjgvbqrdL6lXoOv5SglPGcdgQ-HQbE8NLb1KmNT8Y2Tf7J0CeFKRGSQYRkRq_eoevQxzbHy5RgDHOEUabonjIxpBStOy6DoNrVpP7VpHY1qV1N2fbx_yBH02spGbjYA9l9VLHgpWQl-Qs_HZh5</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2475526121</pqid></control><display><type>article</type><title>Association of NOTCH2NLC Repeat Expansions With Parkinson Disease</title><source>MEDLINE</source><source>American Medical Association Journals</source><creator>Ma, Dongrui ; Tan, Yi Jayne ; Ng, Adeline S. L ; Ong, Helen L ; Sim, Weiying ; Lim, Weng Khong ; Teo, Jing Xian ; Ng, Ebonne Y. L ; Lim, Ee-Chien ; Lim, Ee-Wei ; Chan, Ling-Ling ; Tan, Louis C. S ; Yi, Zhao ; Tan, Eng-King</creator><creatorcontrib>Ma, Dongrui ; Tan, Yi Jayne ; Ng, Adeline S. L ; Ong, Helen L ; Sim, Weiying ; Lim, Weng Khong ; Teo, Jing Xian ; Ng, Ebonne Y. L ; Lim, Ee-Chien ; Lim, Ee-Wei ; Chan, Ling-Ling ; Tan, Louis C. S ; Yi, Zhao ; Tan, Eng-King</creatorcontrib><description>IMPORTANCE: The presence of Notch homolog 2 N-terminal-like C (NOTCH2NLC) repeat expansions are associated with neuronal intranuclear inclusion body disease (NIID), with varied neurological signs, including neuropathy, ataxia, parkinsonism, and tremor. To date, genetic screening of NOTCH2NLC GGC repeats in a cohort with typical Parkinson disease (PD) appears not to have been reported. OBJECTIVE: To investigate if NOTCH2NLC GGC expansions are present in a cohort of patients with PD and controls. DESIGN, SETTING, AND PARTICIPANTS: This case-control study was conducted in 2 tertiary movement disorder centers in Singapore. Participants were recruited and followed up from January 2005 to January 2020. The presence of NOTCH2NLC GGC expansion repeats was screened using polymerase chain reaction tests, and representative samples were verified with long-read genome sequencing. MAIN OUTCOMES AND MEASURES: Qualitative and quantitative comparisons between participants with sporadic PD, healthy control participants, and individuals with NIID. RESULTS: A total of 2076 participants, including 1000 with sporadic PD (600 men [60.0%]; mean age at onset, 62.6 [7.7] years) and 1076 healthy controls (581 men [54.0%]; mean age at study recruitment, 54.9 [9.4] years) were recruited. A total of 13 patients with PD and no healthy control participants were identified as carrying NOTCH2NLC GGC repeat expansions of more than 40 units; the frequency of more than 40 repeat expansions was higher in participants with PD than controls (P < .001). None of the patients with PD were carriers of known PD-associated genes. Ten patients with PD carried a GGC expansion of between 41 and 64 repeats (1% of patients with sporadic PD; mean [SD], 49.4 [9.2] repeats). The other 3 patients carried GGC repeats of 79 or more units, 2 with 122 and 79 repeats, respectively, exhibited typical parkinsonism and were responsive to small dosages of levodopa over many years, with no clinical or imaging features of NIID. The other patient with PD, who had 130 repeats, only developed cognitive impairment before death. Within the GGC expansions, there was no GGA interruptions (mean [SD] GGA percentage in the 3 patients with PD vs patients with NIID, 0% vs 12% [9%]), and the frequency of AGC interruptions was 3 times higher in these patients with PD than patients with NIID (mean [SD], 25% [12%] vs 8% [8%]). CONCLUSIONS AND RELEVANCE: This study demonstrated that individuals with sporadic PD who carried pathogenic NOTCH2NLC GGC repeat expansions can present with typical parkinsonism, requiring only low dosages of levodopa, without displaying other clinical or imaging features of NIID even after several years of follow-up. None of the patients with PD had GGA interruptions within their GGC expansions, and the frequency of AGC interruptions was much higher than that of patients with NIID. The functional significance of a higher moderate repeat expansion in patients with PD compared with healthy controls needs to be further investigated.</description><identifier>ISSN: 2168-6149</identifier><identifier>EISSN: 2168-6157</identifier><identifier>DOI: 10.1001/jamaneurol.2020.3023</identifier><identifier>PMID: 32852534</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Aged ; Antidepressants ; Ataxia ; Brain diseases ; Brief Report ; Case-Control Studies ; Cognitive ability ; Comments ; Expansion ; Female ; Gene sequencing ; Genetic screening ; Genomes ; Homology ; Humans ; Intranuclear Inclusion Bodies ; Levodopa ; Male ; Medical imaging ; Middle Aged ; Movement disorders ; Neurodegenerative Diseases ; Neuropathy ; Online First ; Parkinson Disease - genetics ; Parkinson's disease ; Polymerase chain reaction ; Receptor, Notch2 - genetics ; Tremor ; Trinucleotide Repeat Expansion</subject><ispartof>Archives of neurology (Chicago), 2020-12, Vol.77 (12), p.1559-1563</ispartof><rights>Copyright American Medical Association Dec 2020</rights><rights>Copyright 2020 American Medical Association. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a455t-a16bc93ec291d6edfdb681870ff82376466feb65b3d0984c1dc4652f12477dfc3</citedby><cites>FETCH-LOGICAL-a455t-a16bc93ec291d6edfdb681870ff82376466feb65b3d0984c1dc4652f12477dfc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jamaneurology/articlepdf/10.1001/jamaneurol.2020.3023$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2020.3023$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,776,780,881,3327,27901,27902,76231,76234</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32852534$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Dongrui</creatorcontrib><creatorcontrib>Tan, Yi Jayne</creatorcontrib><creatorcontrib>Ng, Adeline S. L</creatorcontrib><creatorcontrib>Ong, Helen L</creatorcontrib><creatorcontrib>Sim, Weiying</creatorcontrib><creatorcontrib>Lim, Weng Khong</creatorcontrib><creatorcontrib>Teo, Jing Xian</creatorcontrib><creatorcontrib>Ng, Ebonne Y. L</creatorcontrib><creatorcontrib>Lim, Ee-Chien</creatorcontrib><creatorcontrib>Lim, Ee-Wei</creatorcontrib><creatorcontrib>Chan, Ling-Ling</creatorcontrib><creatorcontrib>Tan, Louis C. S</creatorcontrib><creatorcontrib>Yi, Zhao</creatorcontrib><creatorcontrib>Tan, Eng-King</creatorcontrib><title>Association of NOTCH2NLC Repeat Expansions With Parkinson Disease</title><title>Archives of neurology (Chicago)</title><addtitle>JAMA Neurol</addtitle><description>IMPORTANCE: The presence of Notch homolog 2 N-terminal-like C (NOTCH2NLC) repeat expansions are associated with neuronal intranuclear inclusion body disease (NIID), with varied neurological signs, including neuropathy, ataxia, parkinsonism, and tremor. To date, genetic screening of NOTCH2NLC GGC repeats in a cohort with typical Parkinson disease (PD) appears not to have been reported. OBJECTIVE: To investigate if NOTCH2NLC GGC expansions are present in a cohort of patients with PD and controls. DESIGN, SETTING, AND PARTICIPANTS: This case-control study was conducted in 2 tertiary movement disorder centers in Singapore. Participants were recruited and followed up from January 2005 to January 2020. The presence of NOTCH2NLC GGC expansion repeats was screened using polymerase chain reaction tests, and representative samples were verified with long-read genome sequencing. MAIN OUTCOMES AND MEASURES: Qualitative and quantitative comparisons between participants with sporadic PD, healthy control participants, and individuals with NIID. RESULTS: A total of 2076 participants, including 1000 with sporadic PD (600 men [60.0%]; mean age at onset, 62.6 [7.7] years) and 1076 healthy controls (581 men [54.0%]; mean age at study recruitment, 54.9 [9.4] years) were recruited. A total of 13 patients with PD and no healthy control participants were identified as carrying NOTCH2NLC GGC repeat expansions of more than 40 units; the frequency of more than 40 repeat expansions was higher in participants with PD than controls (P < .001). None of the patients with PD were carriers of known PD-associated genes. Ten patients with PD carried a GGC expansion of between 41 and 64 repeats (1% of patients with sporadic PD; mean [SD], 49.4 [9.2] repeats). The other 3 patients carried GGC repeats of 79 or more units, 2 with 122 and 79 repeats, respectively, exhibited typical parkinsonism and were responsive to small dosages of levodopa over many years, with no clinical or imaging features of NIID. The other patient with PD, who had 130 repeats, only developed cognitive impairment before death. Within the GGC expansions, there was no GGA interruptions (mean [SD] GGA percentage in the 3 patients with PD vs patients with NIID, 0% vs 12% [9%]), and the frequency of AGC interruptions was 3 times higher in these patients with PD than patients with NIID (mean [SD], 25% [12%] vs 8% [8%]). CONCLUSIONS AND RELEVANCE: This study demonstrated that individuals with sporadic PD who carried pathogenic NOTCH2NLC GGC repeat expansions can present with typical parkinsonism, requiring only low dosages of levodopa, without displaying other clinical or imaging features of NIID even after several years of follow-up. None of the patients with PD had GGA interruptions within their GGC expansions, and the frequency of AGC interruptions was much higher than that of patients with NIID. The functional significance of a higher moderate repeat expansion in patients with PD compared with healthy controls needs to be further investigated.</description><subject>Aged</subject><subject>Antidepressants</subject><subject>Ataxia</subject><subject>Brain diseases</subject><subject>Brief Report</subject><subject>Case-Control Studies</subject><subject>Cognitive ability</subject><subject>Comments</subject><subject>Expansion</subject><subject>Female</subject><subject>Gene sequencing</subject><subject>Genetic screening</subject><subject>Genomes</subject><subject>Homology</subject><subject>Humans</subject><subject>Intranuclear Inclusion Bodies</subject><subject>Levodopa</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Middle Aged</subject><subject>Movement disorders</subject><subject>Neurodegenerative Diseases</subject><subject>Neuropathy</subject><subject>Online First</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson's disease</subject><subject>Polymerase chain reaction</subject><subject>Receptor, Notch2 - genetics</subject><subject>Tremor</subject><subject>Trinucleotide Repeat Expansion</subject><issn>2168-6149</issn><issn>2168-6157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtrGzEUhUVIiI3rPxBCGcimG7t6S7MpGOfRgnFCSOlSaDRSLHc8cqSZ0v77ythxm2gjwfnO5R4dAC4RnCII0ee13ujW9jE0UwwxnBKIyQkYYsTlhCMmTo9vWg7AOKU1zEdCSAk9BwOCJcOM0CGYzVIKxuvOh7YIrljeP82_4uViXjzardVdcfN7q9uU1VT88N2qeNDxp29Tpq99sjrZD-DM6SbZ8eEege-3N3nIZHF_920-W0w0ZaybaMQrUxJrcIlqbmtXV1wiKaBzEhPBKefOVpxVpIalpAbVhnKGHcJUiNoZMgJf9nO3fbWxtbFtF3WjttFvdPyjgvbqrdL6lXoOv5SglPGcdgQ-HQbE8NLb1KmNT8Y2Tf7J0CeFKRGSQYRkRq_eoevQxzbHy5RgDHOEUabonjIxpBStOy6DoNrVpP7VpHY1qV1N2fbx_yBH02spGbjYA9l9VLHgpWQl-Qs_HZh5</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Ma, Dongrui</creator><creator>Tan, Yi Jayne</creator><creator>Ng, Adeline S. L</creator><creator>Ong, Helen L</creator><creator>Sim, Weiying</creator><creator>Lim, Weng Khong</creator><creator>Teo, Jing Xian</creator><creator>Ng, Ebonne Y. L</creator><creator>Lim, Ee-Chien</creator><creator>Lim, Ee-Wei</creator><creator>Chan, Ling-Ling</creator><creator>Tan, Louis C. S</creator><creator>Yi, Zhao</creator><creator>Tan, Eng-King</creator><general>American Medical Association</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>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20201201</creationdate><title>Association of NOTCH2NLC Repeat Expansions With Parkinson Disease</title><author>Ma, Dongrui ; Tan, Yi Jayne ; Ng, Adeline S. L ; Ong, Helen L ; Sim, Weiying ; Lim, Weng Khong ; Teo, Jing Xian ; Ng, Ebonne Y. L ; Lim, Ee-Chien ; Lim, Ee-Wei ; Chan, Ling-Ling ; Tan, Louis C. S ; Yi, Zhao ; Tan, Eng-King</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a455t-a16bc93ec291d6edfdb681870ff82376466feb65b3d0984c1dc4652f12477dfc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Antidepressants</topic><topic>Ataxia</topic><topic>Brain diseases</topic><topic>Brief Report</topic><topic>Case-Control Studies</topic><topic>Cognitive ability</topic><topic>Comments</topic><topic>Expansion</topic><topic>Female</topic><topic>Gene sequencing</topic><topic>Genetic screening</topic><topic>Genomes</topic><topic>Homology</topic><topic>Humans</topic><topic>Intranuclear Inclusion Bodies</topic><topic>Levodopa</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Middle Aged</topic><topic>Movement disorders</topic><topic>Neurodegenerative Diseases</topic><topic>Neuropathy</topic><topic>Online First</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson's disease</topic><topic>Polymerase chain reaction</topic><topic>Receptor, Notch2 - genetics</topic><topic>Tremor</topic><topic>Trinucleotide Repeat Expansion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Dongrui</creatorcontrib><creatorcontrib>Tan, Yi Jayne</creatorcontrib><creatorcontrib>Ng, Adeline S. L</creatorcontrib><creatorcontrib>Ong, Helen L</creatorcontrib><creatorcontrib>Sim, Weiying</creatorcontrib><creatorcontrib>Lim, Weng Khong</creatorcontrib><creatorcontrib>Teo, Jing Xian</creatorcontrib><creatorcontrib>Ng, Ebonne Y. L</creatorcontrib><creatorcontrib>Lim, Ee-Chien</creatorcontrib><creatorcontrib>Lim, Ee-Wei</creatorcontrib><creatorcontrib>Chan, Ling-Ling</creatorcontrib><creatorcontrib>Tan, Louis C. S</creatorcontrib><creatorcontrib>Yi, Zhao</creatorcontrib><creatorcontrib>Tan, Eng-King</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Archives of neurology (Chicago)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Dongrui</au><au>Tan, Yi Jayne</au><au>Ng, Adeline S. L</au><au>Ong, Helen L</au><au>Sim, Weiying</au><au>Lim, Weng Khong</au><au>Teo, Jing Xian</au><au>Ng, Ebonne Y. L</au><au>Lim, Ee-Chien</au><au>Lim, Ee-Wei</au><au>Chan, Ling-Ling</au><au>Tan, Louis C. S</au><au>Yi, Zhao</au><au>Tan, Eng-King</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of NOTCH2NLC Repeat Expansions With Parkinson Disease</atitle><jtitle>Archives of neurology (Chicago)</jtitle><addtitle>JAMA Neurol</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>77</volume><issue>12</issue><spage>1559</spage><epage>1563</epage><pages>1559-1563</pages><issn>2168-6149</issn><eissn>2168-6157</eissn><abstract>IMPORTANCE: The presence of Notch homolog 2 N-terminal-like C (NOTCH2NLC) repeat expansions are associated with neuronal intranuclear inclusion body disease (NIID), with varied neurological signs, including neuropathy, ataxia, parkinsonism, and tremor. To date, genetic screening of NOTCH2NLC GGC repeats in a cohort with typical Parkinson disease (PD) appears not to have been reported. OBJECTIVE: To investigate if NOTCH2NLC GGC expansions are present in a cohort of patients with PD and controls. DESIGN, SETTING, AND PARTICIPANTS: This case-control study was conducted in 2 tertiary movement disorder centers in Singapore. Participants were recruited and followed up from January 2005 to January 2020. The presence of NOTCH2NLC GGC expansion repeats was screened using polymerase chain reaction tests, and representative samples were verified with long-read genome sequencing. MAIN OUTCOMES AND MEASURES: Qualitative and quantitative comparisons between participants with sporadic PD, healthy control participants, and individuals with NIID. RESULTS: A total of 2076 participants, including 1000 with sporadic PD (600 men [60.0%]; mean age at onset, 62.6 [7.7] years) and 1076 healthy controls (581 men [54.0%]; mean age at study recruitment, 54.9 [9.4] years) were recruited. A total of 13 patients with PD and no healthy control participants were identified as carrying NOTCH2NLC GGC repeat expansions of more than 40 units; the frequency of more than 40 repeat expansions was higher in participants with PD than controls (P < .001). None of the patients with PD were carriers of known PD-associated genes. Ten patients with PD carried a GGC expansion of between 41 and 64 repeats (1% of patients with sporadic PD; mean [SD], 49.4 [9.2] repeats). The other 3 patients carried GGC repeats of 79 or more units, 2 with 122 and 79 repeats, respectively, exhibited typical parkinsonism and were responsive to small dosages of levodopa over many years, with no clinical or imaging features of NIID. The other patient with PD, who had 130 repeats, only developed cognitive impairment before death. Within the GGC expansions, there was no GGA interruptions (mean [SD] GGA percentage in the 3 patients with PD vs patients with NIID, 0% vs 12% [9%]), and the frequency of AGC interruptions was 3 times higher in these patients with PD than patients with NIID (mean [SD], 25% [12%] vs 8% [8%]). CONCLUSIONS AND RELEVANCE: This study demonstrated that individuals with sporadic PD who carried pathogenic NOTCH2NLC GGC repeat expansions can present with typical parkinsonism, requiring only low dosages of levodopa, without displaying other clinical or imaging features of NIID even after several years of follow-up. None of the patients with PD had GGA interruptions within their GGC expansions, and the frequency of AGC interruptions was much higher than that of patients with NIID. The functional significance of a higher moderate repeat expansion in patients with PD compared with healthy controls needs to be further investigated.</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>32852534</pmid><doi>10.1001/jamaneurol.2020.3023</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Archives of neurology (Chicago), 2020-12, Vol.77 (12), p.1559-1563 |
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| source | MEDLINE; American Medical Association Journals |
| subjects | Aged Antidepressants Ataxia Brain diseases Brief Report Case-Control Studies Cognitive ability Comments Expansion Female Gene sequencing Genetic screening Genomes Homology Humans Intranuclear Inclusion Bodies Levodopa Male Medical imaging Middle Aged Movement disorders Neurodegenerative Diseases Neuropathy Online First Parkinson Disease - genetics Parkinson's disease Polymerase chain reaction Receptor, Notch2 - genetics Tremor Trinucleotide Repeat Expansion |
| title | Association of NOTCH2NLC Repeat Expansions With Parkinson Disease |
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