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Screening of GNAL variants in Brazilian patients with isolated dystonia reveals a novel mutation with partial loss of function.
Dos Santos, Camila Oliveira; Masuho, Ikuo; da Silva-Júnior, Francisco Pereira; Barbosa, Egberto Reis; Silva, Sonia Maria Cesar Azevedo; Borges, Vanderci; Ferraz, Henrique Ballalai; Rocha, Maria Sheila Guimarães; Limongi, João Carlos Papaterra; Martemyanov, Kirill A; de Carvalho Aguiar, Patricia.
Afiliação
  • Dos Santos CO; Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Sao Paulo, SP, Brazil.
  • Masuho I; Hospital Israelita Albert Einstein, Av Albert Einstein 627, Bloco A, 2SS IIEP, Sao Paulo, SP, 05652-900, Brazil.
  • da Silva-Júnior FP; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, USA.
  • Barbosa ER; Department of Neurology, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
  • Silva SM; Department of Neurology, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
  • Borges V; Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Sao Paulo, SP, Brazil.
  • Ferraz HB; Hospital do Servidor Público Estadual, Sao Paulo, Sao Paulo, SP, Brazil.
  • Rocha MS; Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Sao Paulo, SP, Brazil.
  • Limongi JC; Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Sao Paulo, SP, Brazil.
  • Martemyanov KA; Hospital Santa Marcelina Sao Paulo, Sao Paulo, SP, Brazil.
  • de Carvalho Aguiar P; Department of Neurology, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
J Neurol ; 263(4): 665-8, 2016 Apr.
Article em En | MEDLINE | ID: mdl-26810727
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Distúrbios Distônicos / Subunidades alfa de Proteínas de Ligação ao GTP / Mutação Tipo de estudo: Diagnostic_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Limite: Adolescent / Adult / Aged / Aged80 / Child / Child, preschool / Female / Humans / Male / Middle aged País/Região como assunto: America do sul / Brasil Idioma: En Revista: J Neurol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Distúrbios Distônicos / Subunidades alfa de Proteínas de Ligação ao GTP / Mutação Tipo de estudo: Diagnostic_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Limite: Adolescent / Adult / Aged / Aged80 / Child / Child, preschool / Female / Humans / Male / Middle aged País/Região como assunto: America do sul / Brasil Idioma: En Revista: J Neurol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha