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

• Published in: BMC neurology Vol. 25; no. 1
• Main Authors: Ramakrishnan, Subasree, Arshad, Faheem, Keerthana, B. S., Bosco, Susan, Gokul Pon, Arun, Ganaraja, V. H., Madhusudhan, Deekshitha, Mahima, R., Arunachal, Gautham, Kulanthaivelu, Karthick, Alladi, Suvarna
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 27.08.2025; BioMed Central
• Subjects: Development and progression; Gene mutations; Genes; Genetic aspects; Nervous system diseases; India
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-025-04336-9

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. 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). Among 86 patients with FTD who underwent WES, seven had MAPT mutations. Notably, two are novel variants. 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.