New THAP1 mutation and role of putative modifier in TOR1A

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• The prevalence of DYT1 (TOR1A gene mutation) and DYT6 (THAP1 gene mutation) can differ across populations, impacting clinical research.
• Understanding genetic variations in dystonia is crucial for accurate diagnosis and treatment strategies.

Purpose of the Study:

• To characterize Brazilian patients with inherited, isolated dystonia.
• To determine the frequency of DYT1 and DYT6 mutations in this cohort.

Main Methods:

• Movement disorder specialists evaluated 78 patients with idiopathic isolated dystonia.
• Sequencing of the TOR1A and THAP1 genes was performed on 68 subjects.

Main Results:

• No deleterious mutations in the TOR1A gene (DYT1) were found. The rs1801968 (TOR1A p.D216H) variant showed no phenotypic association (P = 0.3387).
• One potentially deleterious THAP1 mutation (DYT6), a novel 10-bp deletion (g.5308_5317del), was identified in 1.47% (1/68) of patients.
• The patient cohort's clinical presentation aligned with international dystonia literature.

Conclusions:

• The classical DYT1 mutation is absent in the studied Brazilian dystonia population.
• A novel, potentially deleterious THAP1 mutation associated with DYT6 was discovered.
• The rs1801968 variant in TOR1A is not associated with dystonia in this cohort.