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. 2022 Jul;37(7):1547-1554.
doi: 10.1002/mds.29074. Epub 2022 Jun 20.

Highlighting the Dystonic Phenotype Related to GNAO1

Thomas Wirth  1   2   3 , Giacomo Garone  4   5 , Manju A Kurian  6 , Amélie Piton  2   3   7 , Francisca Millan  8 , Aida Telegrafi  8 , Nathalie Drouot  3 , Gabrielle Rudolf  1   2   3 , Jamel Chelly  2   3   7 , Warren Marks  9 , Lydie Burglen  10 , Diane Demailly  11 , Phillipe Coubes  11 , Mayte Castro-Jimenez  12 , Sylvie Joriot  13 , Jamal Ghoumid  14 , Jérémie Belin  15 , Jean-Marc Faucheux  16 , Lubov Blumkin  17 , Mariam Hull  18 , Mered Parnes  18 , Claudia Ravelli  19 , Gaëtan Poulen  11 , Nadège Calmels  2   3   7 , Andrea H Nemeth  20 , Martin Smith  20 , Angela Barnicoat  21 , Claire Ewenczyk  22   23 , Aurélie Méneret  22   23 , Emmanuel Roze  22   23 , Boris Keren  22   23 , Cyril Mignot  22   23 , Christophe Beroud  24 , Fernando Acosta Jr  9 , Catherine Nowak  25 , William G Wilson  26 , Dora Steel  6 , Alessandro Capuano  5 , Marie Vidailhet  22   23 , Jean-Pierre Lin  27 , Christine Tranchant  1   2   3 , Laura Cif  11 , Diane Doummar  19 , Mathieu Anheim  1   2   3
Affiliations

Highlighting the Dystonic Phenotype Related to GNAO1

Thomas Wirth et al. Mov Disord. 2022 Jul.

Abstract

Background: Most reported patients carrying GNAO1 mutations showed a severe phenotype characterized by early-onset epileptic encephalopathy and/or chorea.

Objective: The aim was to characterize the clinical and genetic features of patients with mild GNAO1-related phenotype with prominent movement disorders.

Methods: We included patients diagnosed with GNAO1-related movement disorders of delayed onset (>2 years). Patients experiencing either severe or profound intellectual disability or early-onset epileptic encephalopathy were excluded.

Results: Twenty-four patients and 1 asymptomatic subject were included. All patients showed dystonia as prominent movement disorder. Dystonia was focal in 1, segmental in 6, multifocal in 4, and generalized in 13. Six patients showed adolescence or adulthood-onset dystonia. Seven patients presented with parkinsonism and 3 with myoclonus. Dysarthria was observed in 19 patients. Mild and moderate ID were present in 10 and 2 patients, respectively.

Conclusion: We highlighted a mild GNAO1-related phenotype, including adolescent-onset dystonia, broadening the clinical spectrum of this condition. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: GNAO1; dystonia; mutation; phenotypes.

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Figures

FIG. 1
FIG. 1
Impact of the mutations on the protein. (A) Position of the variant sites on the heterotrimeric complex containing the Gα subunit. The heterotrimer is depicted in the resting state (GDP‐bound, PDBcode 1GG2). Subunits α, β, and γ are colored in green, cyan, and gray, respectively. Affected residues in this cohort are in red, and their position is indicated both on the human Gαo1 and on rat Gαi1 (UniProtKB ID P10824, between brackets). GDP‐binding residues are colored in yellow. Previously reported GNAO1 variants are in blue. On the right, a focused view of the GDP‐binding site is shown. (B) Cartoon model of the heterotrimeric‐αβγ G‐protein coupled‐receptor on the synaptic cleft. (C) Schematic representation of the disease‐causing variants on GNAO1 transcript (NM_020988.3) and protein (UniprotKB ID P09471‐1). The amino acids impacted by the mutations identified in this work are in red, whereas previously reported variants are in black. The blue bar on the transcript indicates the translated region. The blue segments in the protein sequence indicate the G‐motifs (containing the nucleotide binding residues)—numbered from 1 to 5. Molecular graphics are realized with UCSF Chimera (http://www.rbvi.ucsf.edu/chimera), developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41‐GM103311. The cartoon has been created with BioRender.com. aa, amino acids; nt, nucleotides; UTR, untranslated region. [Color figure can be viewed at wileyonlinelibrary.com]
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References

    1. Nakamura K, Kodera H, Akita T, Shiina M, Kato M, Hoshino H, et al. De novo mutations in GNAO1, encoding a Gαo subunit of heterotrimeric G proteins, cause epileptic encephalopathy. Am J Hum Genet 2013;93(3):496–505. - PMC - PubMed
    1. Schirinzi T, Garone G, Travaglini L, Vasco G, Galosi S, Rios L, et al. Phenomenology and clinical course of movement disorder in GNAO1 variants: results from an analytical review. Parkinsonism Relat Disord 2019;61:19–25. - PubMed
    1. Kulkarni N, Tang S, Bhardwaj R, Bernes S, Grebe TA. Progressive movement disorder in brothers carrying a GNAO1 mutation responsive to deep brain stimulation. J Child Neurol 2016;31(2):211–214. - PubMed
    1. Danti FR, Galosi S, Romani M, Montomoli M, Carss KJ, Raymond FL, et al. GNAO1 encephalopathy: broadening the phenotype and evaluating treatment and outcome. Neurol Genet 2017;3(2):e143 - PMC - PubMed
    1. Feng H, Khalil S, Neubig RR, Sidiropoulos C. A mechanistic review on GNAO1‐associated movement disorder. Neurobiol Dis 2018;116:131–141. - PubMed

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