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Association between trinucleotide CAG repeats of the DNA polymerase gene (POLG) with age of onset of Iranian Friedreich’s ataxia patients

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Abstract

Friedreich’s ataxia (FRDA), an autosomal recessive neurodegenerative disorder, is in most cases due to a homozygous intronic expansion resulting in the loss of function of frataxin. As mitochondrial DNA (mtDNA) copy number has been decreased in FRDA cells and mtDNA polymerase (POLG) is involved in the replication of mtDNA, we searched a trinucleotide CAG repeat length of this enzyme. The POLG CAG repeat length was determined in DNA samples extracted from 20 FRDA patients and 49 control subjects. Our findings showed that the distribution of the POLG CAG repeat length in the patients’ samples matched the distribution for control samples, but we found a statistically significant inverse correlation (r=−0.81) between the POLG CAG repeats and age of onset in FRDA patients. Our results suggest POLG CAG repeat instability would constitute a predisposing factor that, in combination with environmental risk factors, affect age of onset and disease progression.

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Authors and Affiliations

  1. Dept. of Genetic, Science School, Tarbiat Modares University (TMU), Tehran, Iran

    Mohammad Mehdi Heidari & Mehri Khatami

  2. Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, (NIGEB), Karaj Highway, Bolvare Pajoohesh, 14155-6343, Tehran, Iran

    Massoud Houshmand

  3. Special Medical Center, Tehran, Iran

    Massoud Houshmand

  4. Dept. of Biochemical, Science School, Tarbiat Modares University (TMU), Tehran, Iran

    Saman Hosseinkhani

  5. Department of Neurology, Medical Science, Tehran University, Tehran, Iran

    Shahriar Nafissi

  6. Department of Medical Chemistry, Medical University of Vienna, Vienna, Austria

    Barbara Scheiber-Mojdehkar

Authors
  1. Mohammad Mehdi Heidari
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  2. Massoud Houshmand
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  3. Saman Hosseinkhani
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  4. Shahriar Nafissi
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  5. Barbara Scheiber-Mojdehkar
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  6. Mehri Khatami
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Correspondence to Massoud Houshmand.

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Heidari, M.M., Houshmand, M., Hosseinkhani, S. et al. Association between trinucleotide CAG repeats of the DNA polymerase gene (POLG) with age of onset of Iranian Friedreich’s ataxia patients. Neurol Sci 29, 489–493 (2008). https://doi.org/10.1007/s10072-008-1026-y

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  • DOI: https://doi.org/10.1007/s10072-008-1026-y

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