Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May;39(5):897-905.
doi: 10.1002/mds.29752. Epub 2024 Mar 4.

Rare Missense Variants in KCNJ10 Are Associated with Paroxysmal Kinesigenic Dyskinesia

Thomas Wirth  1   2   3 , Emmanuel Roze  4   5 , Clarisse Delvallée  1   2   3 , Oriane Trouillard  5 , Nathalie Drouot  3 , Philippe Damier  6 , Clotilde Boulay  1 , Marine Bourgninaud  4   5 , Prasanthi Jegatheesan  4   5 , Aude Sangare  4   5 , Sylvie Forlani  4   5 , Bertrand Gaymard  4   5 , Remi Hervochon  7 , Vincent Navarro  4   5 , Nadège Calmels  3   8 , Audrey Schalk  3   8 , Christine Tranchant  1   2   3 , Amélie Piton  2   3   8 , Aurélie Méneret  4   5 , Mathieu Anheim  1   2   3
Affiliations

Rare Missense Variants in KCNJ10 Are Associated with Paroxysmal Kinesigenic Dyskinesia

Thomas Wirth et al. Mov Disord. 2024 May.

Abstract

Background: Although the group of paroxysmal kinesigenic dyskinesia (PKD) genes is expanding, the molecular cause remains elusive in more than 50% of cases.

Objective: The aim is to identify the missing genetic causes of PKD.

Methods: Phenotypic characterization, whole exome sequencing and association test were performed among 53 PKD cases.

Results: We identified four causative variants in KCNJ10, already associated with EAST syndrome (epilepsy, cerebellar ataxia, sensorineural hearing impairment and renal tubulopathy). Homozygous p.(Ile209Thr) variant was found in two brothers from a single autosomal recessive PKD family, whereas heterozygous p.(Cys294Tyr) and p.(Thr178Ile) variants were found in six patients from two autosomal dominant PKD families. Heterozygous p.(Arg180His) variant was identified in one additional sporadic PKD case. Compared to the Genome Aggregation Database v2.1.1, our PKD cohort was significantly enriched in both rare heterozygous (odds ratio, 21.6; P = 9.7 × 10-8) and rare homozygous (odds ratio, 2047; P = 1.65 × 10-6) missense variants in KCNJ10.

Conclusions: We demonstrated that both rare monoallelic and biallelic missense variants in KCNJ10 are associated with PKD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: KCNJ10; dystonia; exome; genetics; paroxysmal kinesigenic dyskinesia.

PubMed Disclaimer

References

    1. Bruno MK, Hallett M, Gwinn‐Hardy K, Sorensen B, Considine E, Tucker S, et al. Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria. Neurology 2004;63(12):2280–2287.
    1. Méneret A, Roze E. Paroxysmal movement disorders: an update. Rev Neurol 2016;172(8–9):433–445.
    1. Garone G, Capuano A, Travaglini L, Graziola F, Stregapede F, Zanni G, et al. Clinical and genetic overview of paroxysmal movement disorders and episodic ataxias. Int J Mol Sci 2020;21(10):3603.
    1. van Vliet R, Breedveld G, de Rijk‐van AJ, Brilstra E, Verbeek N, Verschuuren‐Bemelmans C, et al. PRRT2 phenotypes and penetrance of paroxysmal kinesigenic dyskinesia and infantile convulsions. Neurology 2012;79(8):777–784.
    1. Méneret A, Grabli D, Depienne C, Gaudebout C, Picard F, Dürr A, et al. PRRT2 mutations: a major cause of paroxysmal kinesigenic dyskinesia in the European population. Neurology 2012;79(2):170–174.

Substances

Supplementary concepts

Grants and funding

LinkOut - more resources