A Novel Co-existence of Spinocerebellar Ataxia 1 and Spinocerebellar Ataxia 2 Mutations in Indian Patients

Pooja Sharma; Akhilesh K Sonakar; Vinay Goel; Ajay Garg; Achal K Srivastava; Mohammed Faruq

doi:10.1002/mdc3.13464

A Novel Co-existence of Spinocerebellar Ataxia 1 and Spinocerebellar Ataxia 2 Mutations in Indian Patients

Mov Disord Clin Pract. 2022 May 10;9(5):688-692. doi: 10.1002/mdc3.13464. eCollection 2022 Jul.

Authors

Pooja Sharma^{1

2}, Akhilesh K Sonakar³, Vinay Goel⁴, Ajay Garg⁴, Achal K Srivastava³, Mohammed Faruq^{1

2}

Affiliations

¹ Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road Delhi India.
² Academy for Scientific and Innovative Research Ghaziabad India.
³ Neurology Department, Neuroscience Centre All India Institute of Medical Sciences New Delhi India.
⁴ Neuroradiology Department, Neuroscience Centre All India Institute of Medical Sciences New Delhi India.

Abstract

Background: Spinocerebellar ataxia 1 (SCA1) and SCA2 are dominantly inherited ataxias caused due to CAG expansion mutation in ATXN1 (CAG≥39) and ATXN2 (CAG≥32) genes located at 6p22.3 and 12q24.12 loci, respectively, with key manifestations of progressive limb and gait ataxia and with or without brain stem and pyramidal tract involvement. Both SCA1 and SCA2 are quite prevalent subtypes among the SCAs. There are very few reports that describe a combinatorial SCA subtype mutation in a single patient.

Cases: Here, we report a novel co-occurrence of SCA1 and SCA2 mutations in two unrelated patients. Case-1 was observed to carry ATXN1-CAG (30/40) and ATXN2-CAG (23/45), while case-2 harbored ATXN1-CAG (29/42) and ATXN2-CAG (23/41). Overall, the clinical outcome was complex with probable early onset than expected in Case-1 and in Case-2, we observed a significant delayed onset of the disease than expected.

Conclusion: These cases highlight the probabilistic interactive outcome of two unrelated genetic events towards a converging phenotype.

Keywords: SCA; SCA and India; SCA combinatorial mutations; spino cerebellar ataxias; two‐in‐one mutations.

Publication types

Case Reports