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We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature. A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed. Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively. There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype. © 2020 European Academy of Neurology.


Pilar Gómez-Garre, Silvia Jesús, María Teresa Periñán, Astrid Adarmes, Araceli Alonso-Canovas, Alberto Blanco-Ollero, Dolores Buiza-Rueda, Fátima Carrillo, María José Catalán-Alonso, Javier Del Val, Francisco Escamilla-Sevilla, Raúl Espinosa-Rosso, María Carmen Fernández-Moreno, José Manuel García-Moreno, Pedro José García-Ruiz, Sandra Giacometti-Silveira, Javier Gutiérrez-García, Eva López-Valdés, Daniel Macías-García, Juan Carlos Martínez-Castrillo, Irene Martínez-Torres, María Pilar Medialdea-Natera, Adolfo Mínguez-Castellanos, Miguel Ángel Moya, Juan José Ochoa-Sepulveda, Tomás Ojea, Nuria Rodríguez, Miriam Sillero-Sánchez, Cristina Tejera-Parrado, Pablo Mir. Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review. European journal of neurology. 2021 Apr;28(4):1188-1197

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PMID: 33175450

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