Whole genome sequencing for the genetic diagnosis of heterogenous dystonia phenotypes

Introduction: Dystonia is a clinically and genetically heterogeneous disorder and a genetic cause is often difficult to elucidate. This is the first study to use whole genome sequencing (WGS) to investigate dystonia in a large sample of affected individuals. Methods: WGS was performed on 111 probands with heterogenous dystonia phenotypes. We performed analysis for coding and non-coding variants, copy number variants (CNVs), and structural variants (SVs). We assessed for an association between dystonia and 10 known dystonia risk variants. Results: A genetic diagnosis was obtained for 11.7% (13/111) of individuals. We found that a genetic diagnosis was more likely in those with an earlier age at onset, younger age at testing, and a combined dystonia phenotype. We identified pathogenic/likely-pathogenic variants in ADCY5 (n = 1), ATM (n = 1), GNAL (n = 2), GLB1 (n = 1), KMT2B (n = 2), PRKN (n = 2), PRRT2 (n = 1), SGCE (n = 2), and THAP1 (n = 1). CNVs were detected in 3 individuals. We found an association between the known risk variant ARSG rs11655081 and dystonia (p = 0.003). Conclusion: A genetic diagnosis was found in 11.7% of individuals with dystonia. The diagnostic yield was higher in those with an earlier age of onset, younger age at testing, and a combined dystonia phenotype. WGS may be particularly relevant for dystonia given that it allows for the detection of CNVs, which accounted for 23% of the genetically diagnosed cases. © 2019 The Author

Gestión del conocimiento: perspectiva multidisciplinaria. Volumen 12

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 12, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro cuenta con el apoyo de los grupos de investigación: Universidad Sur del Lago “Jesús María Semprúm” (UNESUR), Zulia – Venezuela; Universidad Politécnica Territorial de Falcón Alonso Gamero (UPTAG), Falcón – Venezuela; Universidad Politécnica Territorial de Mérida Kleber Ramírez (UPTM), Mérida – Venezuela; Universidad Guanajuato (UG) - Campus Celaya - Salvatierra - Cuerpo Académico de Biodesarrollo y Bioeconomía en las Organizaciones y Políticas Públicas (C.A.B.B.O.P.P), Guanajuato – México; Centro de Altos Estudios de Venezuela (CEALEVE), Zulia – Venezuela, Centro Integral de Formación Educativa Especializada del Sur (CIFE - SUR) - Zulia - Venezuela, Centro de Investigaciones Internacionales SAS (CIN), Antioquia - Colombia.y diferentes grupos de investigación del ámbito nacional e internacional que hoy se unen para estrechar vínculos investigativos, para que sus aportes científicos formen parte de los libros que se publiquen en formatos digital e impreso

Overweight is more prevalent in patients with Parkinson's disease

Underweight and malnutrition are well documented in Parkinson's disease (PD), while overweight has been less reported. We carried out a cross-sectional study including 177 healthy controls and 177 PD patients attending a tertiary care center. We recorded weight and height for all participants. A statistically significant difference was found in body mass index (BMI) between controls and PD patients (29.1±5.4 versus 27.2±4.7, p<0.001). In the PD Group, two patients were underweight, 32.7% were within normal range, 46.9% had overweight, and 19.2% were obese. Overweight and normal weight were more prevalent in the PD Group (p=<0.01 and <0.001, respectively) when compared to controls. In conclusion, overweight/obesity are common among patients with PD, while underweight is almost negligible

Low specificity and sensitivity of smell identification testing for the diagnosis of Parkinson?s disease

Objective: The aim of this study is to determine if the University of Pennsylvania’s Smell Identification Test (UPSIT) is an accurate diagnostic tool for olfactory dysfunction in Parkinson’s disease (PD). Method: We included 138 non-demented PD subjects and 175 control subjects matched by gender. Smell identification was tested using UPSIT. Results: The mean number of UPSIT items correctly identified by controls was 27.52±5.88; the mean score for PD subjects was 19.66±6.08 (p=<0.001). UPSIT sensitivity was 79.7% with a specificity of 68.5% using a cut-off score of ≤25. The overall accuracy for the diagnosis of PD was of 75.3%. Conclusion: UPSIT accuracy and specificity were lower than what has been previously reported. Our data demonstrates that 17.5% of items of the UPSIT were not well identified by healthy controls. Further research of the identification of a truly cross-cultural test is warranted

Myoclonus-dystonia caused by GNB1 mutation responsive to deep brain stimulation

[Extract] Myoclonus-dystonia is commonly caused by mutations in SGCE, but other genotypes including ADCY5 and KCTD17 mutations have been recently described.1, 2 We report the first patient with myoclonus-dystonia caused by a Guanine nucleotide-binding protein, beta-1 (GNB1) mutation who responded to bilateral globus pallidus interna (GPi) deep brain stimulation (DBS)