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Case Reports
. 2024 Jun;11(6):1636-1642.
doi: 10.1002/acn3.52064. Epub 2024 May 3.

POLR3A-related disorders: From spastic ataxia to generalised dystonia and long-term efficacy of deep brain stimulation

Wai Yan Yau  1 , Catherine Ashton  2 , Eoin Mulroy  3 , Thomas Foltynie  3 , Patricia Limousin  4 , Jana Vandrovcova  5 , Kunal P Verma  6   7   8 , Rick Stell  1 , Mark Davis  9 , Phillipa Lamont  2
Affiliations
Case Reports

POLR3A-related disorders: From spastic ataxia to generalised dystonia and long-term efficacy of deep brain stimulation

Wai Yan Yau et al. Ann Clin Transl Neurol. 2024 Jun.

Abstract

While biallelic POLR3A loss-of-function variants are traditionally linked to hypomyelinating leukodystrophy, patients with a specific splice variant c.1909+22G>A manifest as adolescent-onset spastic ataxia without overt leukodystrophy. In this study, we reported eight new cases, POLR3A-related disorder with c.1909+22 variant. One of these patients showed expanded phenotypic spectrum of generalised dystonia and her sister remained asymptomatic except for hypodontia. Two patients with dystonic arm tremor responded to deep brain stimulation. In our systemic literature review, we found that POLR3A-related disorder with c.1909+22 variant has attenuated disease severity but frequency of dystonia and upper limb tremor did not differ among genotypes.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Archimedean spiral of patient D1 with DBS on/off (A–D); denture of patient D2 with insert showing her one of her small teeth (E); MRI head coronal FLAIR of patient F1 showing SCP sign (F), patient D1 showing pyramidal tract hyperintensities (G), and patient C1 showing splenium of corpus callosum hyperintensities (H).
Figure 2
Figure 2
Comparison of (A) clinical features and (B) radiological features between individuals with and without the splice variant. **** denotes p < 0.001.
See this image and copyright information in PMC

References

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Publication types

Supplementary concepts