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Role of Dynamic and Mitochondrial Mutations in Neurodegenerative Diseases with Ataxia: Lower Repeats and LNAs at Multiple Loci as Alternative Pathogenesis

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Abstract

Spinocerebellar ataxia is a growing group of hereditary neurodegenerative diseases for which ≥30 different genetic loci have been identified. In this study, we assessed the repeats at eight spinocerebellar ataxia (SCA) loci in 188 clinical SCA patients and 100 individuals without any neurological signs. Results from the present study were able to identify 16/188 (8.5 %) clinical ataxia patients with repeat expansions in the pathological range of SCA genes, with the majority having expansion at the SCA1, 2, and 3 loci. The present study further evaluated two mitochondrial mutations associated with ataxia, i.e., T8993G and A8344G. Six patients were identified with A8344G mutation and none had the mutation in ATPase 6 gene; however, G8994A variation was found in three cases. Overall, three cases had triplet repeat expansions as well as mitochondrial (mt) mutations, which indicates potential association of triplet repeat expansions and mitochondrial mutations. Both the molecular analysis of several SCA loci and two relevant mt mutations indicated that the majority of ataxia cases were still undiagnosed; hence, the following hypotheses were proposed and tested based on available data: (i) lower repeats than normal range and (ii) large normal alleles (LNAs) at multiple loci may be an alternative basis for disease pathogenesis.

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Authors and Affiliations

  1. Department of Genetics, Mahavir Hospital, AC Guards, Hyderabad, 500 004, India

    Waseem Gul Lone

  2. Department of Genetics, Osmania University, Hyderabad, 500 007, India

    Waseem Gul Lone & Kaipa Prabhakar Rao

  3. Department of Genetics and Molecular Medicine, Kamineni Hospitals, LB Nagar, Hyderabad, 500 068, India

    Waseem Gul Lone, Subhadra Poornima & Qurratulain Hasan

  4. Department of Neurology, Nizam’s Institute of Medical Sciences, Panjagutta, Hyderabad, 500 082, India

    Angmuthu Kanikannan Meena

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  1. Waseem Gul Lone
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  2. Subhadra Poornima
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  3. Angmuthu Kanikannan Meena
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  4. Kaipa Prabhakar Rao
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  5. Qurratulain Hasan
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Correspondence to Qurratulain Hasan.

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Gul Lone, W., Poornima, S., Meena, A.K. et al. Role of Dynamic and Mitochondrial Mutations in Neurodegenerative Diseases with Ataxia: Lower Repeats and LNAs at Multiple Loci as Alternative Pathogenesis. J Mol Neurosci 54, 837–847 (2014). https://doi.org/10.1007/s12031-014-0431-3

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  • DOI: https://doi.org/10.1007/s12031-014-0431-3

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