New THAP1 mutation and role of putative modifier in TOR1A.

OBJECTIVES: The 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. METHODS: Two movement disorder specialists examined 78 patients with idiopathic isolated dystonia using a standardized questionnaire, before sequencing TOR1A and THAP1 genes. RESULTS: Clinically, 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). CONCLUSIONS: Although 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.

Use of digital panoramic radiography as an auxiliary means of low bone mineral density detection in post-menopausal women.

OBJECTIVES: To correlate the radiomorphometric indices obtained using digital panoramic radiography (DPR) with bone mineral densities, evaluated by the dual-energy X-ray absorptiometry test, in a population of post-menopausal females to identify patients with asymptomatic low bone mineral densities. METHODS: The morphology of the mandibular cortex was evaluated using the mandibular cortical index (MCI) and the inferior mandibular cortex width was evaluated using the mental index (MI) in 64 female patients who had undergone dual-energy X-ray absorptiometry assessment. Of these patients, 21 were diagnosed with osteopaenia and 20 with osteoporosis, and 23 were normal. Three new indices for evaluating the inferior mandibular cortex width were designed: the mental posterior index 1 (MPI1), MPI2 and MPI3. Statistical analyses were performed using the χ(2) and Kruskal-Wallis tests and the receiver operating characteristic curve. RESULTS: There were significant differences between the normal and lower bone mineral density groups (osteopaenia and osteoporosis) for MCI (p < 0.01). In the osteoporosis group, the MI, MPI1, MPI2 and MPI3 were significantly different from the normal and osteopaenia groups (p < 0.05). The MI, MPI1, MPI2 and MPI3 showed that there is an area in the mandibular cortex, located between the mental foramen and the antegonial region, which is valid for identifying females at high risk for osteoporosis. CONCLUSIONS: The MCI, MI, MPI1, MPI2, and MPI3 radiomorphometric indices evaluated using DPR can be used to identify post-menopausal females with low bone densities and to provide adequate medical treatment for them.