Subasree Ramakrishnan, Faheem Arshad, B S Keerthana, Susan Bosco, Arun Gokul Pon, V H Ganaraja, Deekshitha Madhusudhan, R Mahima, Gautham Arunachal, Karthick Kulanthaivelu, Suvarna Alladi
{"title":"使用全外显子组测序检测额颞叶痴呆致病性MAPT基因突变的临床特征、萎缩和遗传模式:来自印度的单中心首次报告。","authors":"Subasree Ramakrishnan, Faheem Arshad, B S Keerthana, Susan Bosco, Arun Gokul Pon, V H Ganaraja, Deekshitha Madhusudhan, R Mahima, Gautham Arunachal, Karthick Kulanthaivelu, Suvarna Alladi","doi":"10.1186/s12883-025-04336-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/objectives: </strong>Frontotemporal Dementia (FTD) is one of the common causes of early-onset degenerative dementia and is a clinically and pathologically heterogeneous group of neurodegenerative disorders. Globally, Microtubule Associated Protein Tau (MAPT), progranulin (GRN), and Chromosome 9 open reading frame 72(C9orf72) are the common FTD genetic mutations. However, they have not been reported from India, and only one progranulin (PGRN) mutation has been reported so far. This study aims to describe the clinical features and radiological patterns of seven patients of FTD harbouring pathogenic MAPT mutations from an Indian cohort of Frontotemporal dementia, using whole-exome sequencing (WES) for the first time.</p><p><strong>Methods: </strong>Subjects with dementia fulfilling the criteria for frontotemporal dementia were recruited from a teaching university hospital in South India. All of them underwent detailed clinical evaluation, neuroimaging, and genetic analysis by Whole Exome Sequencing (WES).</p><p><strong>Results: </strong>Among 86 patients with FTD who underwent WES, seven had MAPT mutations. Notably, two are novel variants.</p><p><strong>Conclusion: </strong>In the Indian context, pathogenic MAPT in FTD is being reported for the first time and notably from a single center by WES. Identifying pathogenic MAPT genes is important in planning mutation-specific clinical trials and understanding ethical and cultural differences in genetic FTD inheritance.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"25 1","pages":"353"},"PeriodicalIF":2.2000,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382150/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clinical profile, atrophy and inheritance patterns of pathogenic MAPT gene mutations in Frontotemporal dementia detected using whole exome sequencing: a single-center first report from India.\",\"authors\":\"Subasree Ramakrishnan, Faheem Arshad, B S Keerthana, Susan Bosco, Arun Gokul Pon, V H Ganaraja, Deekshitha Madhusudhan, R Mahima, Gautham Arunachal, Karthick Kulanthaivelu, Suvarna Alladi\",\"doi\":\"10.1186/s12883-025-04336-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/objectives: </strong>Frontotemporal Dementia (FTD) is one of the common causes of early-onset degenerative dementia and is a clinically and pathologically heterogeneous group of neurodegenerative disorders. Globally, Microtubule Associated Protein Tau (MAPT), progranulin (GRN), and Chromosome 9 open reading frame 72(C9orf72) are the common FTD genetic mutations. However, they have not been reported from India, and only one progranulin (PGRN) mutation has been reported so far. This study aims to describe the clinical features and radiological patterns of seven patients of FTD harbouring pathogenic MAPT mutations from an Indian cohort of Frontotemporal dementia, using whole-exome sequencing (WES) for the first time.</p><p><strong>Methods: </strong>Subjects with dementia fulfilling the criteria for frontotemporal dementia were recruited from a teaching university hospital in South India. All of them underwent detailed clinical evaluation, neuroimaging, and genetic analysis by Whole Exome Sequencing (WES).</p><p><strong>Results: </strong>Among 86 patients with FTD who underwent WES, seven had MAPT mutations. Notably, two are novel variants.</p><p><strong>Conclusion: </strong>In the Indian context, pathogenic MAPT in FTD is being reported for the first time and notably from a single center by WES. Identifying pathogenic MAPT genes is important in planning mutation-specific clinical trials and understanding ethical and cultural differences in genetic FTD inheritance.</p>\",\"PeriodicalId\":9170,\"journal\":{\"name\":\"BMC Neurology\",\"volume\":\"25 1\",\"pages\":\"353\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-08-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382150/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12883-025-04336-9\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12883-025-04336-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Clinical profile, atrophy and inheritance patterns of pathogenic MAPT gene mutations in Frontotemporal dementia detected using whole exome sequencing: a single-center first report from India.
Background/objectives: Frontotemporal Dementia (FTD) is one of the common causes of early-onset degenerative dementia and is a clinically and pathologically heterogeneous group of neurodegenerative disorders. Globally, Microtubule Associated Protein Tau (MAPT), progranulin (GRN), and Chromosome 9 open reading frame 72(C9orf72) are the common FTD genetic mutations. However, they have not been reported from India, and only one progranulin (PGRN) mutation has been reported so far. This study aims to describe the clinical features and radiological patterns of seven patients of FTD harbouring pathogenic MAPT mutations from an Indian cohort of Frontotemporal dementia, using whole-exome sequencing (WES) for the first time.
Methods: Subjects with dementia fulfilling the criteria for frontotemporal dementia were recruited from a teaching university hospital in South India. All of them underwent detailed clinical evaluation, neuroimaging, and genetic analysis by Whole Exome Sequencing (WES).
Results: Among 86 patients with FTD who underwent WES, seven had MAPT mutations. Notably, two are novel variants.
Conclusion: In the Indian context, pathogenic MAPT in FTD is being reported for the first time and notably from a single center by WES. Identifying pathogenic MAPT genes is important in planning mutation-specific clinical trials and understanding ethical and cultural differences in genetic FTD inheritance.
期刊介绍:
BMC Neurology is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of neurological disorders, as well as related molecular genetics, pathophysiology, and epidemiology.