Session Information
Date: Tuesday, June 21, 2016
Session Title: Genetics (NON-PD)
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To study the frequency and spectrum of GNAL genetic variations in a large population of isolated dystonia (DT) patients from Spain.
Background: GNAL encodes the stimulatory alpha subunit (Gαolf) of a GTP-binding protein important for dopamine D1 receptor function and olfactory signal transduction. In brain, GNAL presents the alternative use of upstream promoters and first exons, giving rise to two different proteins, the normal Gαolf isoform and an extra-large variant known as XL- Gαolf. Mutations in GNAL have been associated with autosomal dominant adult-onset cranio-cervical DT, with incomplete penetrance. The frequency of GNAL mutations from different populations varies from 0.3% (in Caucasian patients) to 2% (in Asian patients).
Methods: We screened for mutations all exons, the exon/intron boundaries, and the 5’UTR regions of both GNAL isoforms expressed I brain by HRM analysis. Samples showing abnormal melting profiles were subsequently sequenced on both strands. We included 820 unrelated patients with adult-onset isolated DT (30% men, mean age of 60±15 years, mean age at onset 47±17 years). Of these patients, 585 had focal DT (306 blepharospasm, 199 cervical DT, 37 writer’s cramp, and 14 laryngeal DT), 120 segmental DT, 22 multifocal DT, 31 generalized DT, 64, dystonic tremor and 11 other DT. In addition, in order to determinate the frequency and spectrum of the variations presented in our healthy population, we included in the analysis a cohort of 307 unrelated healthy controls (40.7% men, mean age of 55.8±15.2 years). The impact of the DNA variants was evaluated by in-silico analysis using several computational tools (Variant annotation Integrator and Variant Effect Predictor). Promoter mutation’s function was predicted by CONSITE software.
Results: We detected a total of 21 variants across GNAL sequence, including 6 in 5’UTR, 7 intronic, and 8 in coding region (5 missense, and 3 synonymous). The in-silico analysis revealed that 3 GNAL genetic variants were potentially deleterious. These variants were found in a single case of DT each one. Therefore, the frequency of GNAL mutations in our population was 0.49%.
Conclusions: Our study offers a complete and exhaustive molecular analysis of GNAL variants in isolated DT patients. GNAL mutations in isolated DT patients from Spain are rare.
Yes. Preliminary results were presented in the LXVII annual meeting of the Spanish Society of Neurology.
To cite this abstract in AMA style:
P. Gómez-Garre, I. Huertas-Fernández, M.T. Cáceres-Redondo, A. Alonso-Canovas, I. Bernal-Bernal, A. Blanco-Ollero, M. Bonilla-Toribio, J.A. Burguera, M. Carballo, F. Carrillo, M.J. Catalán-Alonso, F. Escamilla-Sevilla, R. Espinosa-Rosso, M.C. Fernández-Moreno, J. García-Caldentey, J.M. García-Moreno, S. Giacometti-Silveira, J. Gutiérrez-García, S. Jesús-Maestre, E. López-Valdés, J.C. Martínez-Castrillo, M.P. Medialdea-Natera, C. Méndez-Lucena, A. Mínguez-Castellanos, M. Moya, J.J. Ochoa-Sepúlveda, T. Ojea, N. Rodríguez, I. Rubio-Agusti, M. Sillero-Sánchez, J. del Val, L. Vargas-González, P. Mir. Mutational analysis of GNAL gene in isolated dystonia patients from Spain [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/mutational-analysis-of-gnal-gene-in-isolated-dystonia-patients-from-spain/. Accessed June 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/mutational-analysis-of-gnal-gene-in-isolated-dystonia-patients-from-spain/