Camila Oliveira dos Santos, Ikuo Masuho, Francisco Pereira da Silva-Júnior, Egberto Reis Barbosa, Sonia Maria Cesar Azevedo Silva, Vanderci Borges, Henrique Ballalai Ferraz, Maria Sheila Guimarães Rocha, João Carlos Papaterra Limongi, Kirill A. Martemyanov, Patricia de Carvalho Aguiar
J Neurol.. 2016 Apr;263(4): 665-8.
http://link.springer.com/article/10.1007%2Fs00415-016-8026-2
Abstract
GNAL was identified as a cause of dystonia in patients from North America, Europe and Asia. In this study, we aimed to investigate the prevalence of GNAL variants in Brazilian patients with dystonia. Ninety-one patients with isolated idiopathic dystonia, negative for THAP1 and TOR1A mutations, were screened for GNAL variants by Sanger sequencing. Functional characterization of the Gαolf protein variant was performed using the bioluminescence resonance energy transfer assay. A novel heterozygous nonsynonymous variant (p. F133L) was identified in a patient with cervical and laryngeal dystonia since the third decade of life, with no family history. This variant was not identified in healthy Brazilian controls and was not described in 63,000 exomas of the ExAC database. The F133L mutant exhibited significantly elevated levels of basal BRET and severely diminished amplitude of response elicited by dopamine, that both indicate substantial functional impairment of Gαolf in transducing receptor signals, which could be involved in dystonia pathophysiology. GNAL mutations are not a common cause of dystonia in the Brazilian population and have a lower prevalence than THAP1 and TOR1A mutations. We present a novel variant that results in partial Gαolf loss of function.