Objective: To explore the role of mtHaplogroups in early and late onset SCA2 patients.

Background: An unstable expansion of a CAG tract in the ATXN2 gene causes ADCAs known as Spinocerebellar ataxia type 2(SCA2). The age at onset modifiers of various neurodegenerative diseases, including SCA 2, have been associated to mitochondrial dysfunction. In SCA2 expanded CAG repeats not entirely explains age at onset, this shows the existence of other disease modifiers of age onset. The clinical manifestations of mitochondrial DNA haplogroups in polyglutamine disease suggest that they may play as disease modifiers in SCA-2.

Method: We sequenced the D-LOOP and hypervariable regions of the mitochondrial genome in 123 early and late onset (70 and 53, respectively) individuals from Indian population to examine the role of mtDNA haplogroups in age at onset variance in SCA2 patients. On the basis of the age of onset and CAG repeat number, we divided SCA2 patients in two groups. Total Five years of onset gap was taken between the Early-onset and late-onset group in SCA2 patients on the same CAG repeat size.

Results: We obtained the major haplogroups H,L,U, M,A,N,J,I,T,R,D, W, and D. The frequency of each haplogroup in the early-onset and late-onset groups were H(35.71%), L(4.29%), U (14.29%), W(1.43%), M(32.86%), G(1.43%), A(1.43%), N(7.14%), J(1.43%) and H(28.30%), L(3.77%), U(7.55. %), M(39.62%), A(1.89%), N(1.89%), J(1.89%), I(3.77%), T(5.6 %), R (1.89%), D(1.89%) respectively. The two mtDNA haplogroups H and M were found to most prevalent in both early-onset and late-onset SCA2 patient groups according to the frequency distribution. In the group of early-onset SCA2 patients, the frequency of the H and M mtDNA haplogroups were 53.19% and 46.81%, respectively. On otherhand, the frequency distribution of the H and M mtDNA haplogroups was 41.67% and 58.33%, respectively, in patients with late-onset SCA2. Further, we considered both the mtDNA haplogroups H and M to rule out as AO modifier factor in SCA2 patients. However, there was no significant association found between mtDNA haplogroup clusters and SCA2 early and late-onset patient’s groups.

Conclusion: These findings suggest that age onset modifiers of SCA2 early and late onset patients the mtDNA haplogroups analysis should perform in worldwide SCA2 patient’s samples to exploration of mtDNA haplogroup role in disease age modifiers variability.

References: References:
1. Ramos A, Planchat M, Vieira Melo AR, Raposo M, Shamim U, Suroliya V, Srivastava AK, Faruq M, Morino H, Ohsawa R, Kawakami H. Mitochondrial DNA haplogroups and age at onset of Machado–Joseph disease/spinocerebellar ataxia type 3: A study in patients from mult iple populations. European Journal of Neurology. 2019 Mar;26(3):506-12.
2. Singh I, Faruq M, Padma MV, Goyal V, Behari M, Grover A, Mukerji M, Srivastava AK. Investigation of mitochondrial DNA variations among Indian Friedreich’s ataxia (FRDA) patients. Mitochondrion. 2015 Nov 1;25:1-5.
3. Sonakar AK, Shamim U, Srivastava MP, Faruq M, Srivastava AK. SCA2 in the Indian population: Unified haplotype and variable phenotypic patterns in a large case series. Parkinsonism & Related Disorders. 2021 Aug 1;89:139-45.
4. Sharma P, Sonakar AK, Tyagi N, Suroliya V, Kumar M, Kutum R, Asokchandran V, Ambawat S, Shamim U, Anand A, Ahmad I. Genetics of Ataxias in Indian Population: A Collative Insight from a Common Genetic Screening Tool. Advanced Genetics. 2022 Jun;3(2):2100078.
5. Sharma P, Sonakar AK, Goel V, Garg A, Srivastava AK, Faruq M. A Novel Co‐existence of Spinocerebellar Ataxia 1 and Spinocerebellar Ataxia 2 Mutations in Indian Patients. Movement Disorders Clinical Practice. 2022 Jul;9(5):688-92.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-of-early-and-late-age-of-onset-with-mitochondrial-dna-haplogroup-in-indian-spinocerebellar-ataxia-type-2-patients/