RFC1 AAGGG repeat expansion masquerading as Chronic Idiopathic Axonal Polyneuropathy

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 Idiopa...

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Vydané v:Journal of neurology Ročník 268; číslo 11; s. 4280 - 4290
Hlavní autori: Tagliapietra, Matteo, Cardellini, Davide, Ferrarini, Moreno, Testi, Silvia, Ferrari, Sergio, Monaco, Salvatore, Cavallaro, Tiziana, Fabrizi, Gian Maria
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2021
Springer Nature B.V
Predmet:
Ataxia
Autonomic nervous system
Biopsy
Cerebellar ataxia
Cerebellum
Medicine
Medicine & Public Health
Neurology
Neuropathy
Neuroradiology
Neurosciences
Original Communication
Patients
Polyneuropathy
Reflexes
Replication factor C
Sensorimotor system
Sural nerve
Vestibular system
Chronic Idiopathic Axonal Neuropathy
Vestibular Areflexia Syndrome
Replication factor C subunit 1
Neuropathy
Cerebellar Ataxia
ISSN:0340-5354, 1432-1459, 1432-1459
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Shrnutí: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 ( τ b  = 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 ( τ b  = − 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.
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ISSN:0340-5354
1432-1459
1432-1459
DOI:10.1007/s00415-021-10552-3