title: Novel THAP1 variants in Brazilian patients with idiopathic isolated dystonia.
abstract: THAP1 mutations are associated with idiopathic isolated dystonia in different ethnicities, but the importance of this gene as a cause of dystonia in the Brazilian population has not been determined. The aim of this study was to investigate the prevalence of THAP1 variants in Brazilian patients with idiopathic dystonia and to describe their clinical characteristics including non-motor symptoms. One hundred and ten unrelated patients with non-TOR1A (DYT1) idiopathic isolated dystonia and family members were evaluated and screened for genetic variants. Variants with a potential pathological role were observed in 9.0% of families studied, of which four were novel. The variants were identified in approximately 12% of patients with the age of onset below 40 years. In most of the patients, the onset of the disease was before early adulthood. The upper limb was the most common site of the onset, and approximately half of the patients had dysphonia. Pain, anxiety, and sleep-onset insomnia were the most prevalent non-motor symptoms, and their prevalence was not different from that observed in THAP1-negative patients. Therefore, THAP1 variants are an important cause of dystonia among individuals with an early-onset disease and a positive family history. The phenotypical heterogeneity among patients carrying similar variants shows that other factors may be modulating the disease.
authors: Department of Neurology, Sao Paulo University Medical School, Sao Paulo, SP, Brazil.
authors: Francisco Pereira
authors: FP
authors: da Silva-Junior
authors: Hospital Israelita Albert Einstein, Sao Paulo, SP, Brazil.
authors: Camila Oliveira
authors: CO
authors: dos Santos
authors: Hospital do Servidor Publico Estadual, Sao Paulo, SP, Brazil; Department of Neurology and Neurosurgery, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.
authors: Sonia Maria Cesar Azevedo
authors: SM
authors: Silva
authors: Department of Neurology, Sao Paulo University Medical School, Sao Paulo, SP, Brazil.
authors: Egberto Reis
authors: ER
authors: Barbosa
authors: Department of Neurology and Neurosurgery, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.
authors: Vanderci
authors: V
authors: Borges
authors: Department of Neurology and Neurosurgery, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.
authors: Henrique Ballalai
authors: HB
authors: Ferraz
authors: Department of Neurology, Sao Paulo University Medical School, Sao Paulo, SP, Brazil.
authors: João Carlos Papaterra
authors: JC
authors: Limongi
authors: Hospital Santa Marcelina, Sao Paulo, SP, Brazil.
authors: Maria Sheila Guimarães
authors: MS
authors: Rocha
authors: Hospital Israelita Albert Einstein, Sao Paulo, SP, Brazil; Department of Neurology and Neurosurgery, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil. Electronic address: patriciamc@einstein.br.
authors: Patricia
authors: P
authors: de Carvalho Aguiar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D020821:Dystonic Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C474080:THAP1 protein, human
keywords: DYT6; Dystonia; Non-motor symptoms; THAP1; TOR1A