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Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies

Affiliations
  • 1Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
  • 2Department of Neurology, University Hospital Basel, University of Basel, Basel 4031, Switzerland.
  • 3Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
  • 4Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
  • 5Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.

Published on:

July 9, 2024

Abstract

Biallelic expansions of the AAGGG repeat in the replication factor C subunit 1 () have recently been described to be responsible for cerebellar ataxia, peripheral neuropathy and vestibular areflexia syndrome. This genetic alteration has also allowed genetic classification in up to one-third of cases with idiopathic sensory neuropathy. Here, we screened a well-characterized cohort of inflammatory neuropathy patients for repeat expansions to explore whether RFC1 was increased from background rates and possibly involved in the pathogenesis of inflammatory neuropathy. A total of 259 individuals with inflammatory neuropathy and 243 healthy controls were screened for the AAGGG repeat expansion using short-range flanking PCR and repeat-primed PCR. Cases without amplifiable PCR product on flanking PCR and positive repeat-primed PCR were also tested for the mostly non-pathogenic expansions of the AAAGG and AAAAG repeat units. None of the patients showed biallelic AAGGG expansion of , and their carrier frequency for AAGGG was comparable with controls [ = 27 (5.2%) and = 23 (4.7%), respectively; > 0.5]. Data suggest that the pathologic expansions of AAGGG repeats do not contribute to the development of inflammatory neuropathies nor lead to misdiagnosed cases. Accordingly, routine genetic screening for repeat expansion is not indicated in this patient population.

Keywords:

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