Sensory neuropathy due to RFC1 in a patient with ALS: more than a coincidence?

Schoeberl, Florian; Schöser, Benedikt; Küpper, Clemens; Voelk, Stefanie; Sonnenfeld, Stefan; Tonon, Matthias; Schaub, Annalisa; Scholz, Veronika; Kleinle, Stephanie; Erdmann, Hannes; Wolf, Dieter A; Reilich, Peter

doi:10.1007/s00415-021-10835-9

Cited by 9 publications

(17 citation statements)

References 13 publications

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“…In addition, the expansion has been detected in a patient with CANVAS and features resembling dementia with Lewy bodies [14]. Upper or lower motor neuron involvement has been found in 24 of 38 patients [11], and a patient with RFC1-associated ALS has recently been reported [9], but the expansion has not been discovered in a large cohort of patients with sporadic ALS [15]. Altogether, studies on patients with diverse phenotypes are needed to further explore the involvement of RFC1 in multisystemic degeneration manifested as heterogeneous neurological symptoms.…”

Section: Discussionmentioning

confidence: 98%

“…A recent study on four CANVAS patients has suggested that RFC1-related ataxia is a multisystemic neurodegenerative disorder affecting also cognitive domains and pyramidal tract neurons [5]. Furthermore, the expansion has been found in patients with other phenotypes, such as multiple system atrophy (MSA), clinically confirmed Parkinson's disease (PD) and motor neuron pathology [6][7][8][9]. We have previously identified nine patients with biallelic (AAGGG) exp in a population-based screening of patients with inherited ataxia or polyneuropathy [10].…”

Section: Introductionmentioning

confidence: 99%

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Cognitive impairment is not uncommon in patients with biallelic RFC1 AAGGG repeat expansion, but the expansion is rare in patients with cognitive disease

Korpioja

Krüger

Hurme-Niiranen

et al. 2022

Parkinsonism & Related Disorders

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Cognitive impairment is not uncommon in patients with biallelic RFC1 AAGGG repeat expansion, but the expansion is rare in patients with cognitive disease

Korpioja

Krüger

Hurme-Niiranen

et al. 2022

Parkinsonism & Related Disorders

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“…Pathological studies confirmed that the degeneration of the dorsal columns occurs in up to half of patients, especially in lumbar regions, including both genetic ( SOD1 ) and sporadic forms [ 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. The predominant involvement of lumbar spinal cord segments in both functional and pathological examinations suggests an axonal length-dependent degeneration, taking as a starting point cortical and subcortical brain structures, as suggested by the corticofugal propagation proposed by Braak [ 77 ].…”

Section: Spinal Ascending Sensory Pathwaysmentioning

confidence: 99%

“…In the familial form of ALS secondary to the p.A382P mutation of the TARBPD gene, a clinical sensory neuronopathy was confirmed by histopathology [ 92 ]. Interestingly, a case has been reported of an ALS patient with sensory neuropathy/neuronopathy and with biallelic RFC1 AAGGG repeat expansion (400) [ 93 ]. RFC1 biallelic expansion is related to CANVAS, a rare genetic disorder characterized by cerebellar ataxia, sensory neuropathy/neuronopathy, and vestibular areflexia.…”

Section: Dorsal Root Ganglia and Dorsal Rootsmentioning

confidence: 99%

Sensory Involvement in Amyotrophic Lateral Sclerosis

Rubio

Herrando-Grabulosa

Navarro

2022

IJMS

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Although amyotrophic lateral sclerosis (ALS) is pre-eminently a motor disease, the existence of non-motor manifestations, including sensory involvement, has been described in the last few years. Although from a clinical perspective, sensory symptoms are overshadowed by their motor manifestations, this does not mean that their pathological significance is not relevant. In this review, we have made an extensive description of the involvement of sensory and autonomic systems described to date in ALS, from clinical, neurophysiological, neuroimaging, neuropathological, functional, and molecular perspectives.

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“…Biallelic RFC1 (AAGGG) exp has also been found in some patients with parkinsonism [4,6]. Furthermore, nonclassical phenotypes, such as multiple system atrophy or amyotrophic lateral sclerosis, have been described [7,8].…”

Section: Introductionmentioning

confidence: 99%

Association of biallelic RFC1 expansion with early‐onset Parkinson's disease

Ylikotila

Sipilä

Alapirtti

et al. 2023

Euro J of Neurology

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Background and Purpose The biallelic repeat expansion (AAGGG)exp in the replication factor C subunit 1 gene (RFC1) is a frequent cause of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) as well as late‐onset ataxia. The clinical spectrum of RFC1 disease has expanded since the first identification of biallelic (AAGGG)exp and includes now various nonclassical phenotypes. Biallelic (AAGGG)exp in RFC1 in patients with clinically confirmed Parkinson's disease (PD) has recently been found. Methods A nationwide cohort of 273 Finnish patients with early‐onset PD was examined for the biallelic intronic expansion in RFC1. The expansion (AAGGG)exp was first screened using extra long polymerase chain reactions (Extra Large‐PCRs) and flanking multiplex PCR. The presence of biallelic (AAGGG)exp was then confirmed by repeat‐primed PCR and, finally, the repeat length was determined by long‐read sequencing. Results Three patients were found with the biallelic (AAGGG)exp in RFC1 giving a frequency of 1.10% (0.23%–3.18%; 95% confidence interval). The three patients fulfilled the diagnostic criteria of PD, none of them had ataxia or neuropathy, and only one patient had a mild vestibular dysfunction. The age at onset of PD symptoms was 40–48 years and their disease course had been unremarkable apart from the early onset. Conclusions Our results suggest that (AAGGG)exp in RFC1 is a rare cause of early‐onset PD. Other populations should be examined in order to determine whether our findings are specific to the Finnish population.

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Sensory neuropathy due to RFC1 in a patient with ALS: more than a coincidence?

Cited by 9 publications

References 13 publications

Cognitive impairment is not uncommon in patients with biallelic RFC1 AAGGG repeat expansion, but the expansion is rare in patients with cognitive disease

Cognitive impairment is not uncommon in patients with biallelic RFC1 AAGGG repeat expansion, but the expansion is rare in patients with cognitive disease

Sensory Involvement in Amyotrophic Lateral Sclerosis

Association of biallelic RFC1 expansion with early‐onset Parkinson's disease

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