Publications

Authors:

Tagliapietra, Matteo; Cardellini, Davide; Ferrarini, Moreno; Testi, Silvia; Ferrari, Sergio; Monaco, Salvatore; Cavallaro, Tiziana; Fabrizi, Gian Maria

Title:

RFC1 AAGGG repeat expansion masquerading as Chronic Idiopathic Axonal Polyneuropathy

Year:

2021

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

A Stampa

Referee:

Sì

Name of journal:

Journal of Neurology

ISSN of journal:

0340-5354

N° Volume:

268

Number or Folder:

11

Page numbers:

4280-4290

Keyword:

Cerebellar Ataxia; Chronic Idiopathic Axonal Neuropathy; Neuropathy; Replication factor C subunit 1; Vestibular Areflexia Syndrome

Short description of contents:

Background: A biallelic intronic AAGGG repeat expansion in the Replication Factor C subunit 1 (RFC1) gene has been recently associated with Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome, a disorder often presenting as a slowly evolving sensory neuropathy at the onset. "Chronic Idiopathic Axonal Polyneuropathy" (CIAP) is a common indolent axonal neuropathy of adulthood which remains without an identifiable cause despite thorough investigations. Methods: We screened 234 probands diagnosed with CIAP for a pathogenic biallelic RFC1 AAGGG repeat expansion. Patients were selected from 594 consecutive patients with neuropathy referred to our tertiary-care center for a sural nerve biopsy over 10 years. Results: The RFC1 AAGGG repeat expansion was common in patients with pure sensory neuropathy (21/40, 53%) and less frequent in cases with predominantly sensory (10/56, 18%, P < 0.001) or sensorimotor (3/138, 2%, P < 0.001) neuropathy. The mutation was associated with sensory ataxia (τb = 0.254, P < 0.001), autonomic disturbances (35% vs 8%, Prevalence Odds Ratio-POR 6.73 CI 95% 2.79-16.2, P < 0.001), retained deep tendon reflexes (score 18.0/24 vs 11.5/24, R = 0.275, P < 0.001). On pathology, we observed absent/scant regenerative changes (τb = - 0.362, P < 0.001), concomitant involvement of large (100% and 99%, n.s.), small myelinated (97% vs 81%, POR 7.74 CI 95% 1.03-58.4, P = 0.02) and unmyelinated nerve fibers (85% vs 41%, POR 8.52 CI 95% 3.17-22.9, P < 0.001). Cerebellar or vestibular involvement was similarly rare in the two groups. Conclusions: This study highlights the frequent occurrence of the RFC1 AAGGG repeat expansion in patients diagnosed with CIAP and characterizes the clinical and pathological features of the related neuro(no)pathy.

Web page:

https://doi.org/10.1007/s00415-021-10552-3

Product ID:

120843

Handle IRIS:

11562/1042498

Last Modified:

November 14, 2022

Bibliographic citation:

Tagliapietra, Matteo; Cardellini, Davide; Ferrarini, Moreno; Testi, Silvia; Ferrari, Sergio; Monaco, Salvatore; Cavallaro, Tiziana; Fabrizi, Gian Maria, RFC1 AAGGG repeat expansion masquerading as Chronic Idiopathic Axonal Polyneuropathy «Journal of Neurology» , vol. 268 , n. 11 , 2021 , pp. 4280-4290

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