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Large Interruptions of GAA Repeat Expansion Mutations in Friedreich Ataxia Are Very Rare

Al-Mahdawi, S; Ging, H; Bayot, A; Cavalcanti, F; La Cognata, V; Cavallaro, S; Giunti, P; (2018) Large Interruptions of GAA Repeat Expansion Mutations in Friedreich Ataxia Are Very Rare. Frontiers in Cellular Neuroscience , 12 , Article 443. 10.3389/fncel.2018.00443. Green open access

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Abstract

Friedreich ataxia is a multi-system autosomal recessive inherited disorder primarily caused by homozygous GAA repeat expansion mutations within intron 1 of the frataxin gene. The resulting deficiency of frataxin protein leads to progressive mitochondrial dysfunction, oxidative stress, and cell death, with the main affected sites being the large sensory neurons of the dorsal root ganglia and the dentate nucleus of the cerebellum. The GAA repeat expansions may be pure (GAA)n in sequence or may be interrupted with regions of non-GAA sequence. To our knowledge, there has been no large-scale study of FRDA patient DNA samples to determine the frequency of large interruptions in GAA repeat expansions. Therefore, we have investigated a panel of 245 Friedreich ataxia patient and carrier DNA samples using GAA repeat PCR amplification and MboII restriction enzyme digestion. We demonstrate that the vast majority (97.8%) of Friedreich ataxia GAA repeat expansion samples do not contain significant sequence changes that would result in abnormal MboII digestion profiles, indicating that they are primarily pure GAA repeats. These results show for the first time that large interruptions in the GAA repeats are very rare.

Type: Article
Title: Large Interruptions of GAA Repeat Expansion Mutations in Friedreich Ataxia Are Very Rare
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fncel.2018.00443
Publisher version: https://doi.org/10.3389/fncel.2018.00443
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/10063273
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