Beijer, Danique;
Dohrn, Maike F;
De Winter, Jonathan;
Fazal, Sarah;
Cortese, Andrea;
Stojkovic, Tanya;
Fernández-Eulate, Gorka;
... Baets, Jonathan; + view all
(2022)
RFC1 repeat expansions: A recurrent cause of sensory and autonomic neuropathy with cough and ataxia.
European Journal of Neurology
, 29
(7)
pp. 2156-2161.
10.1111/ene.15310.
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Abstract
BACKGROUND: Ataxia and cough are rare features in hereditary sensory and autonomic neuropathies (HSAN), a group of diseases of mostly unknown genetic cause. Biallelic repeat expansions in RFC1 are associated with cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). METHODS: After unremarkable whole-exome sequencing (WES) analysis, we performed a repeat-primed PCR to detect intronic RFC1 expansions in 12 HSAN families, which all presented with chronic cough. RESULTS: In these patients, 75% carried biallelic expansions of the pathogenic AAGGG motif. Compared to RFC1-/- cases, RFC1+/+ patients presented more consistently with positive sensory and autonomic symptoms. Afferent ataxia was more severe in the RFC1+/+ cohort and cerebellar ataxia was a common feature (21%). CONCLUSIONS: We demonstrate that RFC1 is a frequent cause of (WES-negative) HSAN with chronic cough and ataxia. The diagnostic yield of RFC1 repeat-primed PCR was surprisingly high, given that HSAN is genetically poorly understood. This combination of symptoms HSAN, ataxia, and chronic cough symptoms represents a new nosological entity within the neuropathy-ataxia spectrum.
| Type: | Article |
|---|---|
| Title: | RFC1 repeat expansions: A recurrent cause of sensory and autonomic neuropathy with cough and ataxia |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/ene.15310 |
| Publisher version: | https://doi.org/10.1111/ene.15310 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | RFC1 repeat-primed PCR, afferent ataxia, autonomic dysfunction, chronic cough, next generation sequencing |
| UCL classification: | 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 > Department of Neuromuscular Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10145678 |
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