JOAO CARLOS PAPATERRA LIMONGI
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
5 resultados
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- Novel THAP1 variants in Brazilian patients with idiopathic isolated dystonia(2014) SILVA-JUNIOR, Francisco Pereira da; SANTOS, Camila Oliveira dos; SILVA, Sonia Maria Cesar Azevedo; BARBOSA, Egberto Reis; BORGES, Vanderci; FERRAZ, Henrique Ballalai; LIMONGI, Joao Carlos Papaterra; ROCHA, Maria Sheila Guimaraes; AGUIAR, Patricia de CarvalhoTHAP1 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.
- The prevalence of PRKRA mutations in idiopathic dystonia(2018) SANTOS, Camila Oliveira dos; SILVA-JUNIOR, Francisco Pereira da; PUGA, Renato David; BARBOSA, Egberto Reis; SILVA, Sonia Maria Cesar Azevedo; BORGES, Vanderci; LIMONGI, Joao Carlos Papaterra; ROCHA, Maria Sheila Guimaraes; FERRAZ, Henrique Ballalai; AGUIAR, Patricia de CarvalhoIntroduction: DYT-PRKRA (DYT16) is considered a rare cause of dystonia-parkinsonism. The significance of this gene as a cause of dystonia and its phenotypical characterization must be determined in larger cohorts. We aimed to investigate the role of PRKRA in patients with dystonia. Methods: We sequenced PRKRA in 153 unrelated Brazilian patients with idiopathic dystonia. The frequency of novel missense variants was investigated in healthy Brazilian controls and in public databases. Homozygosity in the PRKRA region was assessed through polymorphic markers. Results: PRKRA variants were identified in seven probands with isolated dystonia, including a novel c.C795A variant in compound heterozygosity with the previously described c.C665T variant. Heterozygosity in the gene region was observed in two probands who were homozygous for c.C665T, indicating that this mutation originated from independent events, suggesting a hotspot. Conclusion: PRKRA is not an unusual cause of idiopathic dystonia. In this cohort, it was responsible for 4.5% of the total of cases (4.9% of the isolated dystonia cases). The most common phenotype was early onset isolated focal dystonia followed by generalization, parkinsonism was not observed. This is first report of PRKRA causing adulthood-onset dystonia. Screenings of large cohorts are recommended to investigate the role of this gene in isolated dystonia, as well as in dystonia-parkinsonism cases worldwide.
- Non-invasive brain stimulation and kinesiotherapy for treatment of focal dystonia: Instrumental analysis of three cases(2020) SOUZA, Carolina de Oliveira; GOULARDINS, Juliana; COELHO, Daniel Boari; CASAGRANDE, Sara; CONTI, Juliana; LIMONGI, Joao Carlos Papaterra; BARBOSA, Egberto Reis; MONTE-SILVA, Katia; TANAKA, ClariceDystonia is a disabling movement disorder characterized by co-contraction of antagonist and agonist muscles, leading to abnormal sustained postures and impaired motor control. Cervical Dystonia (CD) and Hand Focal Dystonia (HFD) have been the most common forms of focal dystonia (FD). Do Non-Invasive Brain Neuromodulation (NIBS) such as Transcranial Direct Current Stimulation (tDCS) and repetitive Transcranial Magnetic Stimulation (rTMS) modulate the excitability of the connections between the motor cortical areas and may represent a therapeutic alternative for focal dystonia? Herein, we reported three cases of focal dystonia, two of them with cervical dystonia (CD) and one with hand focal dystonia (HFD), treated with NIBS combined to kinesiotherapy. The patients were daily submitted to 15 sessions of NIBS combined simultaneously with kinesiotherapy. CD patients were treated with tDCS (2 mA, 20 min, over the primary motor cortex), and HFD patient with rTMS (1 Hz, 1200 pulses, 80% of resting motor threshold, over the premotor cortex). For the CD patient's assessment, the Modified Toronto Scale for Cervical Dystonia Assessment (MTS), quiet balance test, and visual postural assessment were applied to observe the therapeutic effects. Quality handwriting analysis, tremor acceleration amplitudes, and the Wrinter's Cramp Rating Scale (WCRS) were used to assess the NIBS effect on HFD symptoms. Patients were evaluated before (pretest), immediately after (posttest), and three months after treatment (retention). NIBS associated with kinesiotherapy produced a long-term improvement of dystonia symptoms in all three patients. rTMS and tDCS associated with kinesiotherapy showed to be useful and safe to relief the dystonia symptoms in individuals with different types of focal dystonia with distinct functional disorders. Significance: The combined use of these intervention strategies seems to optimize and anticipate satisfactory clinical results in these neurological conditions, characterized by its difficult clinical management.
- High prevalence of self-reported non-motor symptoms and lack of correlation with motor severity in adult patients with idiopathic isolated dystonia(2022) SILVA-JUNIOR, Francisco Pereira da; ALVES, Camila Oliveira dos Santos; SILVA, Sonia Maria Cesar Azevedo; BORGES, Vanderci; FERRAZ, Henrique Ballalai; ROCHA, Maria Sheila Guimaraes; LIMONGI, Joao Carlos Papaterra; BARBOSA, Egberto Reis; AGUIAR, Patricia de CarvalhoBackground Although abnormal movements and postures are the hallmark of dystonia, non-motor symptoms (NMS) are common and negatively affect quality of life.ObjectivesThe aim of this study was to screen dystonia patients for NMS and analyze their association with clinical parameters, including motor disability. Methods Adult patients with idiopathic isolated dystonia were interviewed and examined. Dystonia severity was evaluated with the Fahn-Marsden Dystonia Rating Scale and the presence of NMS was assessed using a list of 29 complaints. Results A hundred and two patients (63.7% female) were enrolled. Dystonia began after 20 years of age in 61.8% and was focal or segmental in 82.8% of patients. Only eight patients (7.8%) had no NMS and 59.8% reported more than five. The most prevalent NMS were pain (72.5%) and anxiety (63.7%), followed by difficulty recalling information (44.1%), sadness/anhedonia (41.2%), and difficulty falling asleep (38.2%). No correlation was found between the total number of NMS and dystonia severity (p=0.18) or regular botulinum toxin use (p=0.66). The majority of NMS domains correlated with each other. Conclusions Our results confirm a high prevalence of NMS among dystonia patients, even in those with mild motor disability. The pathophysiology of NMS in dystonia remains to be completely understood.
- Screening of GNAL variants in Brazilian patients with isolated dystonia reveals a novel mutation with partial loss of function(2016) SANTOS, Camila Oliveira dos; MASUHO, Ikuo; SILVA-JUNIOR, Francisco Pereira da; BARBOSA, Egberto Reis; SILVA, Sonia Maria Cesar Azevedo; BORGES, Vanderci; FERRAZ, Henrique Ballalai; ROCHA, Maria Sheila Guimaraes; LIMONGI, Joao Carlos Papaterra; MARTEMYANOV, Kirill A.; AGUIAR, Patricia de CarvalhoGNAL was identified as a cause of dystonia in patients from North America, Europe and Asia. In this study, we aimed to investigate the prevalence of GNAL variants in Brazilian patients with dystonia. Ninety-one patients with isolated idiopathic dystonia, negative for THAP1 and TOR1A mutations, were screened for GNAL variants by Sanger sequencing. Functional characterization of the G alpha(olf) protein variant was performed using the bioluminescence resonance energy transfer assay. A novel heterozygous nonsynonymous variant (p. F133L) was identified in a patient with cervical and laryngeal dystonia since the third decade of life, with no family history. This variant was not identified in healthy Brazilian controls and was not described in 63,000 exomas of the ExAC database. The F133L mutant exhibited significantly elevated levels of basal BRET and severely diminished amplitude of response elicited by dopamine, that both indicate substantial functional impairment of G alpha(olf) in transducing receptor signals, which could be involved in dystonia pathophysiology. GNAL mutations are not a common cause of dystonia in the Brazilian population and have a lower prevalence than THAP1 and TOR1A mutations. We present a novel variant that results in partial G alpha(olf) loss of function.