Vikram V Holla, M M Samim, Riyanka Kumari, Debjyoti Dhar, Prashant Phulpagar, Neeharika Sriram, Shweta Prasad, Jitender Saini, Nitish Kamble, Ravi Yadav, Babylakshmi Muthusamy, Pramod Kumar Pal
{"title":"PLA2G6 相关神经变性的临床、放射学和遗传学谱系:一家三级医疗中心的经验","authors":"Vikram V Holla, M M Samim, Riyanka Kumari, Debjyoti Dhar, Prashant Phulpagar, Neeharika Sriram, Shweta Prasad, Jitender Saini, Nitish Kamble, Ravi Yadav, Babylakshmi Muthusamy, Pramod Kumar Pal","doi":"10.5334/tohm.897","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Despite being the second most common type of neurodegeneration with brain iron accumulation, there is limited literature on <i>PLA2G6</i>-associated neurodegeneration (PLAN) within the Asian ethnicity, particularly in the Indian context.</p><p><strong>Methods: </strong>We conducted a retrospective observational study on patients with pathogenic/likely pathogenic <i>PLA2G6</i> variants based on exome sequencing.</p><p><strong>Results: </strong>We identified 26 patients (22 families, 15 males) of genetically-confirmed PLAN with a median age of 22.5 years and age at onset of 13.0 years, encompassing various subtypes: infantile neuroaxonal dystrophy (5/26;19.2%), atypical neuroaxonal dystrophy (3/26;11.5%), dystonia-parkinsonism (5/26;19.2%), dystonia-parkinsonism-myoclonus (n = 4, 15.38%), early-onset Parkinson's disease (2/26;7.7%), complex dystonia (2/26;7.7%), and complicated hereditary spastic paraparesis (cHSP; 5/26;19.2%). The common initial symptoms included walking difficulty (7/26;26.9%), developmental regression (6/26;23.1%), and slowness (4/26;15.4%). Dystonia (14/26;53.8%), followed by parkinsonism (11/26; 42.3%), was the most common motor symptom. Non-motor symptoms included cognitive decline (12/26;46.2%) and behavioral changes (6/26;23.1%). Neuroimaging revealed cerebellar atrophy in 23/26 (88.5%) patients and claval hypertrophy in 80% (4/5) of INAD patients. Levodopa responsiveness was noted in 12 of 14 patients with parkinsonism/dystonia who received levodopa, and dyskinesia was noted in 10/11 patients. Genetic analysis revealed a total of 19 unique variants in <i>PLA2G6</i> gene, of which 11 were novel. Twelve patients harbored the c.2222G>A variant, which is predominantly seen in Asian subpopulations.</p><p><strong>Conclusions: </strong>The study introduces 26 new patients of PLAN and 12 patients associated with the c.2222G>A variant, potentially forming the most extensive single center series to date. It also expands the phenotypic, neuroimaging, and genotypic spectrum of PLAN.</p>","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342831/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Clinical, Radiological and Genetic Spectrum of <i>PLA2G6</i>-Associated Neurodegeneration: An Experience From a Tertiary Center.\",\"authors\":\"Vikram V Holla, M M Samim, Riyanka Kumari, Debjyoti Dhar, Prashant Phulpagar, Neeharika Sriram, Shweta Prasad, Jitender Saini, Nitish Kamble, Ravi Yadav, Babylakshmi Muthusamy, Pramod Kumar Pal\",\"doi\":\"10.5334/tohm.897\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Despite being the second most common type of neurodegeneration with brain iron accumulation, there is limited literature on <i>PLA2G6</i>-associated neurodegeneration (PLAN) within the Asian ethnicity, particularly in the Indian context.</p><p><strong>Methods: </strong>We conducted a retrospective observational study on patients with pathogenic/likely pathogenic <i>PLA2G6</i> variants based on exome sequencing.</p><p><strong>Results: </strong>We identified 26 patients (22 families, 15 males) of genetically-confirmed PLAN with a median age of 22.5 years and age at onset of 13.0 years, encompassing various subtypes: infantile neuroaxonal dystrophy (5/26;19.2%), atypical neuroaxonal dystrophy (3/26;11.5%), dystonia-parkinsonism (5/26;19.2%), dystonia-parkinsonism-myoclonus (n = 4, 15.38%), early-onset Parkinson's disease (2/26;7.7%), complex dystonia (2/26;7.7%), and complicated hereditary spastic paraparesis (cHSP; 5/26;19.2%). The common initial symptoms included walking difficulty (7/26;26.9%), developmental regression (6/26;23.1%), and slowness (4/26;15.4%). Dystonia (14/26;53.8%), followed by parkinsonism (11/26; 42.3%), was the most common motor symptom. Non-motor symptoms included cognitive decline (12/26;46.2%) and behavioral changes (6/26;23.1%). Neuroimaging revealed cerebellar atrophy in 23/26 (88.5%) patients and claval hypertrophy in 80% (4/5) of INAD patients. Levodopa responsiveness was noted in 12 of 14 patients with parkinsonism/dystonia who received levodopa, and dyskinesia was noted in 10/11 patients. Genetic analysis revealed a total of 19 unique variants in <i>PLA2G6</i> gene, of which 11 were novel. Twelve patients harbored the c.2222G>A variant, which is predominantly seen in Asian subpopulations.</p><p><strong>Conclusions: </strong>The study introduces 26 new patients of PLAN and 12 patients associated with the c.2222G>A variant, potentially forming the most extensive single center series to date. It also expands the phenotypic, neuroimaging, and genotypic spectrum of PLAN.</p>\",\"PeriodicalId\":23317,\"journal\":{\"name\":\"Tremor and Other Hyperkinetic Movements\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342831/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tremor and Other Hyperkinetic Movements\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5334/tohm.897\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tremor and Other Hyperkinetic Movements","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5334/tohm.897","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
The Clinical, Radiological and Genetic Spectrum of PLA2G6-Associated Neurodegeneration: An Experience From a Tertiary Center.
Background: Despite being the second most common type of neurodegeneration with brain iron accumulation, there is limited literature on PLA2G6-associated neurodegeneration (PLAN) within the Asian ethnicity, particularly in the Indian context.
Methods: We conducted a retrospective observational study on patients with pathogenic/likely pathogenic PLA2G6 variants based on exome sequencing.
Results: We identified 26 patients (22 families, 15 males) of genetically-confirmed PLAN with a median age of 22.5 years and age at onset of 13.0 years, encompassing various subtypes: infantile neuroaxonal dystrophy (5/26;19.2%), atypical neuroaxonal dystrophy (3/26;11.5%), dystonia-parkinsonism (5/26;19.2%), dystonia-parkinsonism-myoclonus (n = 4, 15.38%), early-onset Parkinson's disease (2/26;7.7%), complex dystonia (2/26;7.7%), and complicated hereditary spastic paraparesis (cHSP; 5/26;19.2%). The common initial symptoms included walking difficulty (7/26;26.9%), developmental regression (6/26;23.1%), and slowness (4/26;15.4%). Dystonia (14/26;53.8%), followed by parkinsonism (11/26; 42.3%), was the most common motor symptom. Non-motor symptoms included cognitive decline (12/26;46.2%) and behavioral changes (6/26;23.1%). Neuroimaging revealed cerebellar atrophy in 23/26 (88.5%) patients and claval hypertrophy in 80% (4/5) of INAD patients. Levodopa responsiveness was noted in 12 of 14 patients with parkinsonism/dystonia who received levodopa, and dyskinesia was noted in 10/11 patients. Genetic analysis revealed a total of 19 unique variants in PLA2G6 gene, of which 11 were novel. Twelve patients harbored the c.2222G>A variant, which is predominantly seen in Asian subpopulations.
Conclusions: The study introduces 26 new patients of PLAN and 12 patients associated with the c.2222G>A variant, potentially forming the most extensive single center series to date. It also expands the phenotypic, neuroimaging, and genotypic spectrum of PLAN.