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. 2021 Feb 9;92(4):444-446.
doi: 10.1136/jnnp-2020-325092. Online ahead of print.

RFC1-related ataxia is a mimic of early multiple system atrophy

Roisin Sullivan #  1 , Wai Yan Yau #  2   3 , Viorica Chelban  2   3 , Salvatore Rossi  4 , Natalia Dominik  2 , Emer O'Connor  2   3 , John Hardy  5 , Nicholas Wood  3   6 , Andrea Cortese  2   3 , Henry Houlden  2   3
Affiliations

RFC1-related ataxia is a mimic of early multiple system atrophy

Roisin Sullivan et al. J Neurol Neurosurg Psychiatry. .
No abstract available

Keywords: cerebellar ataxia; multisystem atrophy; neurogenetics.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Clinical presentation of affected patients. (A) Workflow of RFC1 screen; clinical screening of cohort leads to sample gDNA undergoing flanking PCR and those with no amplifiable product and potential carriers are taken forward for RPPCR. Samples with a positive RPPCR trace (hallmark sawtooth pattern) are then Southern blotted, confirming size of expansion. (B) CANVAS RPPCR positive fragment analysis traces for patients 1, 2 and 3 and a positive CANVAS and negative control. (C) Southern blot results with size of bands indicated; 12 477 and 9434 bp for patient 1 which encompass 953 and 1541 repeat units, 11 244 bp for patient 2 (1315 repeat units) (black dashed lines), 11 244 bp for positive CANVAS control and 5000 bp for negative control. (D) Allelic carrier frequency of different allelic combinations in clinical MSA cohort. Known pathogenic conformation AAGGG/AAGGG underlined. (E) Neuroimaging of patient 1 at age 66 years. (i) MRI head T2 FLAIR axial sequence showed minimal changes in basal ganglia, (ii) DaTscan showed asymmetrical reduction in putaminal dopamine transporter uptake (black arrow), (iii) MRI head T2 axial sequence showed pontine and middle cerebellar peduncle atrophy without ‘hot cross bun’ sign and (iv) MRI head T1 sagittal sequence shows cerebellar and medulla atrophy. (F) Neuroimaging of patient 2 at age 65 years. (i) MRI head T2 FLAIR axial sequence showed normal pontine appearance, (ii) MRI head T1 sagittal sequence showed no evidence of cerebellar or brainstem atrophy and (iii) MRI head T2 FLAIR axial sequence showed normal appearance of basal ganglia. (G) Neuroimaging of patient 3 at age 56 years. (i) MRI head T2 axial sequence showed symmetrical diminution of lentiform nuclei with subtle hyperintensity along dorsolateral aspect of the putamen, (ii) MRI T2 axial sequence showing ‘hot cross bun’ sign and (iii) MRI T1 axial sequence showed pontine and cerebellar atrophy. (H) NCS showed sensory neuronopathy with normal motor studies and mild distal denervation on EMG while for patient 1 and patient 2 showed sensory neuronopathy with normal motor studies. Patient 3 was normal. (11), wild type conformation; bp, base pairs; CANVAS, cerebellar ataxia, neuropathy and vestibular areflexia syndrome; CMAP, compound motor action potential; DML, distal motor latency; EMG, electromyography; gDNA, genomic DNA; MCV, motor conduction velocity; MSA, multiple systems atrophy; MUP, motor unit potentials; N, normal; (n), expanded conformation; NCS, nerve conduction study; RBD, REM sleep behaviour disorder; REM, rapid eye movement; RPPCR, repeat primed PCR; SAP, sensory action potential; TP, tibialis posterior.
See this image and copyright information in PMC

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