Novel THAP1 variants in Brazilian patients with idiopathic isolated dystonia

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.