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

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.