Expanding the phenotypic and genotypic spectrum of DYT-TUBB4A with seven patients from India

Divyani Garg; Vikram V Holla; Jacky Ganguly; Roopa Rajan; Arti Saini; Ayush Agarwal; Divya M Radhakrishnan; Purba Basu; Banashree Mondal; Debjyoti Dhar; Nitish Kamble; Ravi Yadav; Babylakshmi Muthusamy; Hrishikesh Kumar; Achal Kumar Srivastava; Pramod Kumar Pal

doi:10.1016/j.parkreldis.2024.107012

Expanding the phenotypic and genotypic spectrum of DYT-TUBB4A with seven patients from India

Parkinsonism Relat Disord. 2024 May 16:124:107012. doi: 10.1016/j.parkreldis.2024.107012. Online ahead of print.

Authors

Divyani Garg¹, Vikram V Holla², Jacky Ganguly³, Roopa Rajan⁴, Arti Saini⁴, Ayush Agarwal⁴, Divya M Radhakrishnan⁴, Purba Basu³, Banashree Mondal³, Debjyoti Dhar², Nitish Kamble², Ravi Yadav², Babylakshmi Muthusamy⁵, Hrishikesh Kumar³, Achal Kumar Srivastava⁴, Pramod Kumar Pal²

Affiliations

¹ Department of Neurology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: divyanigarg@aiims.edu.
² Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
³ Department of Neurology, Institute of Neurosciences, Kolkata, India.
⁴ Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
⁵ Department of Human Genetics, Manipal Institute of Higher Education, Manipal, India.

PMID: 38762926
DOI: 10.1016/j.parkreldis.2024.107012

Abstract

Background: Variants in the TUBB4A gene are associated with dystonia (DYT-TUBB4A), Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC) and spastic paraplegia. Phenotypes intermediate to these three broad phenotypes are also observed. These are rare disorders, and data from diverse populations remains limited. We report seven Indian cases with dystonia phenotype related to TUBB4A mutation.

Cases: Among these seven patients, age at onset ranged from 5 to 48 years. Five patients had cranio-cervical onset of dystonia. One patient had prominent parkinsonism with dystonia. Patients responded well to botulinum toxin injected for laryngeal, cervical and jaw dystonia. The patient with parkinsonism responded well to levodopa, albeit with development of dyskinesias. Apart from the common p.Arg2Gly variant in three patients with DYT-TUBB4A, other variants included p.Arg262Pro, p.Arg39Cys and p.Asp245Asn.

Conclusions: We report the first collection of cases with TUBB4A mutation from India. We expand the phenotype to include levodopa-responsive parkinsonism. Indian patients, consistent with global literature, harbor prominent adductor dysphonia, cervical and jaw dystonia, which responds well to botulinum treatment.

Keywords: Adductor dysphonia; Dystonia; Hypomyelination; TUBB4A.