New THAP1 mutation and role of putative modifier in TOR1A

Author(s)

Piovesana, L. G. ^[1] ; Torres, F. R. ; Azevedo, P. C. ^[1] ; Amaral, T. P. ^[2] ; Lopes-Cendes, I. ^[2] ; D'Abreu, A.

Affiliation

^[1] Univ Campinas UNICAMP, Dept Med Genet, Campinas, SP - Brazil

^[2] D'Abreu, A., Univ Campinas UNICAMP, Dept Neurol, Campinas, SP, Brazil. Torres, F. R., Univ Campinas UNICAMP, Dept Med Genet, Campinas, SP - Brazil

• Document type: Journal article
• Source: ACTA NEUROLOGICA SCANDINAVICA; v. 135, n. 2, p. 183-188, FEB 2017.
• Web of Science Citations: 1

Abstract

ObjectivesThe prevalence of DYT1 (mutation in TOR1A) and DYT6 (mutation in THAP1) may vary in different populations, which can have important implications in clinical investigation. Our goal was to characterize patients with inherited and isolated dystonia and determine the frequency of mutations responsible for DYT1 and DYT6 in Brazilian patients. MethodsTwo movement disorder specialists examined 78 patients with idiopathic isolated dystonia using a standardized questionnaire, before sequencing TOR1A and THAP1 genes. ResultsClinically, our cohort was similar to those described in the international literature. Molecular studies of 68 subjects revealed only one potentially deleterious variant in THAP1 (1/68 patients, 1.47%). This was a novel 10-bp deletion at the end of exon 1, g.5308\_5317del (ng\_011837.1), which is predicted to create an alternative splicing and the insertion of a premature stop codon. Although we did not observe any potentially deleterious mutations in TOR1A, we found the missense variant rs1801968 (TOR1A p.D216H), previously reported as either a modifier of dystonia phenotype or a predisposing factor for dystonia. However, we did not identify any phenotypic impact related to the missense variant rs1801968 (P = 0.3387). ConclusionsAlthough clinically similar to most cohorts with dystonia worldwide, the classical mutation (c.907\_909delGAG) in TOR1A (causing DYT1) is absent in our patients. However, we found a potentially deleterious THAP1 mutation not previously reported. In addition, we found no association of rs1801968 with dystonia. (AU)

• FAPESP's process: 10/11085-9 - Clinical, genetical and neuroimaging evaluation of dystonias in the brazilian population
• Grantee: Anelyssa Cysne Frota D'Abreu
• Support Opportunities: Research Grants - Young Investigators Grants