A Novel RORA Hinge-Region Variant in Adult IDDECA With Cerebellar Atrophy and Marked Response to Valproate.
Overview
- Università Cattolica del Sacro Cuore Rome Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy
- R&I Genetics Padova Italy
Abstract
Objectives: To expand the RORA mutational and clinical spectrum by reporting a novel hinge‐region variant associated with an adult progressive phenotype and a marked therapeutic response to valproate.
Methods: We describe a 61‐year‐old woman with lifelong intellectual disability who developed subacute severe motor deterioration in adulthood. Evaluation included brain MRI and whole‐exome sequencing.
Results: Whole‐exome sequencing identified a novel heterozygous variant, c.551C>G (p.Pro184Arg), in the hinge region (domain D) of RORA, a region not previously implicated in human disease. While RORA‐related disorders are typically described as neurodevelopmental conditions, our patient showed progressive motor decline with loss of independent ambulation. Brain MRI demonstrated marked vermian atrophy, supporting a possible progressive component. Withdrawal of valproate was followed by severe clinical worsening, whereas reintroduction led to marked improvement in tremor and gait, restoring independent ambulation.
Discussion: This case expands the mutational and phenotypic spectrum of RORA‐related disorders and suggests that hinge‐region variants may contribute to a more severe phenotype. It also supports a role for cortical hyperexcitability in the motor manifestations and highlights a potentially treatable component, with implications for clinical management.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- uniprot.org/
uniprotkb/ , at UniProt; found in the referencesp35398
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 8 keywords, 7 MeSH terms, 13 references.
Cite
This paper
Busco, V., Di Lazzaro, G., Cimmino, A. T., Bove, F., Saccinto, L., Silvestri, G., & Bentivoglio, A. R. (2026). A Novel RORA Hinge-Region Variant in Adult IDDECA With Cerebellar Atrophy and Marked Response to Valproate. European journal of neurology, 33(7), e70699. https://
BibTeX
@article{busco2026novel,
author = {Busco, V. and Di Lazzaro, G. and Cimmino, A. T. and Bove, F. and Saccinto, L. and Silvestri, G. and Bentivoglio, A. R.},
title = {{A Novel RORA Hinge-Region Variant in Adult IDDECA With Cerebellar Atrophy and Marked Response to Valproate}},
journal = {European journal of neurology},
year = {2026},
month = jul,
volume = {33},
number = {7},
pages = {e70699},
publisher = {Wiley},
issn = {1351-5101},
doi = {10.1111/
url = {https://
pmid = {42438296},
pmcid = {PMC13358359}
}
RIS
TY - JOUR
AU - Busco, V.
AU - Di Lazzaro, G.
AU - Cimmino, A. T.
AU - Bove, F.
AU - Saccinto, L.
AU - Silvestri, G.
AU - Bentivoglio, A. R.
TI - A Novel RORA Hinge-Region Variant in Adult IDDECA With Cerebellar Atrophy and Marked Response to Valproate
T2 - European journal of neurology
J2 - Eur J Neurol
PY - 2026
DA - 2026/
VL - 33
IS - 7
SP - e70699
SN - 1351-5101
PB - Wiley
DO - 10.1111/
UR - https://
LA - en
ER -
CSL-JSON
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"container-title": "European journal of neurology",
"author": [
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"URL": "https://
"language": "en",
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