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. 2025 May;12(5):594-601.
doi: 10.1002/mdc3.14325. Epub 2025 Jan 3.

Genetic Landscape of Dystonia in Asian Indians

Arti Saini  1 , Inder Singh  1 , Mukesh Kumar  2 , Divya Madathiparambil Radhakrishnan  1 , Ayush Agarwal  1 , Divyani Garg  1 , Arunmozhimaran Elavarasi  1 , Rahul Singh  1 , Vivek Chouhan  1 , Sandeep  1 , Anu Gupta  1 , Venugopalan Yamuna Vishnu  1 , Mamta Bhushan Singh  1 , Rohit Bhatia  1 , Ajay Garg  3 , Neerja Gupta  4 , Riyaz Ahmad Mir  5 , Mohammed Faruq  2 , Balachandran Krishnamma Binukumar  2 , Achal Kumar Srivastava  1 , Roopa Rajan  1
Affiliations

Genetic Landscape of Dystonia in Asian Indians

Arti Saini et al. Mov Disord Clin Pract. 2025 May.

Abstract

Background: Genomic variations associated with dystonia in Asian Indians remain largely unknown.

Objectives: To identify genomic alterations associated with dystonia in the Asian Indian population using next generation sequencing approaches.

Methods: From September 2018 to December 2023, we enrolled 745 individuals including probands with dystonia and family members, in the Indian Movement Disorder Registry and Biobank. Clinical and demographic data were captured on a REDCap platform. We performed whole exome sequencing (WES) on DNA specimens obtained from 267 individuals with isolated, combined or complex dystonia. Variants were classified according to joint guidelines of American College of Medical Genetics and Genomics (ACMG) and Association of Molecular Pathology (AMP).

Results: The mean age of the WES cohort was 33.8 ± 16.2 years, and mean age at onset (AAO) of dystonia was 25.6 ± 17.7 years. 62.2% had isolated dystonia, 7.9% combined and 29.2% had complex phenotypes. WES identified pathogenic/ likely pathogenic variants in 54 patients (20.2%) including 14 novel variants in known dystonia genes. Variants in THAP1 were most common followed by PANK2, GLB1, PLA2G6, TOR1A, ANO3, VPS16, SGCE, SPG7, FTL and other genes. Multifocal/generalized distribution of dystonia [OR: 4.1; 95% CI 1.4-12.2, P = 0.011] and family history [OR: 4.3; 95% CI 2.1-8.9, P < 0.001] were associated with positive yield on WES.

Conclusion: THAP1 was the most frequent dystonia associated gene in this cohort. Singleton WES identifiedpotentially pathogenic variants in approximately one out of five patients tested, and contributed to management decisions in 4%.

Keywords: Asian Indian; biobank; dystonia; next generation sequencing; whole exome sequencing.

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Conflict of interest statement

Ethical Compliance Statement: This study was approved by the Institutional Ethics Committee, IEC No: 173/06.04.2018, RP‐4/2018 and IEC No: 382/07.06.2019, RP‐22/2019. Written informed consent was obtained from all subjects prior to recruitment. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflict of Interest: This research was funded by Department of Biotechnology (DBT) under the project titled “The Indian Movement Disorder Registry and Biobank: Clinical and Genetic evaluation of movement disorders in Indian patients” and Indian Council of Medical Research (ICMR) under the project titled “Clinical and genetic characterization of spectrum of dystonia using deep targeted clinical sequencing”. Authors report no potential conflicts of interest.

Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report.

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