A rare sequence variant in intron 1 of THAP1 is associated with primary dystonia

Although coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult-onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P < 0.01). Dystonia classification included cervical dystonia (N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw-opening oromandibular dystonia (N = 1), blepharospasm (N = 2), and unclassified (N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform 2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A variant showed extensive apoptosis with relatively fewer cells in the G2 phase of the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate that THAP1 c.71+9C>A is a risk factor for adult-onset primary dystonia

Usefulness of Changes in the Food Safety System – on the Basis of the Audits of NIK, EC and Own Studies

Polski system nadzoru nad bezpieczeństwem żywności jest wieloinstytucjonalny. Powołanie Państwowej Inspekcji Bezpieczeństwa Żywności, dzięki konsolidacji Inspekcji Weterynaryjnej, Państwowej Inspekcji Ochrony Roślin i Nasiennictwa, Inspekcji Jakości Handlowej Artykułów Rolno-Spożywczych oraz przeniesienie do nowego podmiotu części zadań z Państwowej Inspekcji Sanitarnej, Inspekcji Handlowej, a w zakresie dotyczącym kontroli stosowania i składowania nawozów także zadań Inspekcji Ochrony Środowiska, posłużyłoby ujednoliceniu procesów kontrolnych i monitorujących, ograniczyło niejasności kompetencyjne i decyzyjne oraz poprawiło bezpieczeństwo żywności w Polsce. Biorąc pod uwagę wyniki kontroli przeprowadzonych przez Najwyższą Izbę Kontroli oraz audytów Dyrekcji Generalnej ds. Zdrowia i Bezpieczeństwa Żywności Komisji Europejskiej, jak również obserwacje własne, przedstawiono celowość zmian istniejącego systemu kontroli bezpieczeństwa żywności w Polsce.The Polish system for food safety supervision comprises numerous institutions. The establishment of the State Food Safety Inspectorate (Polish: Państwowa Inspekcja Bezpieczeństwa Żywności), thanks to consolidation of the Veterinary Inspectorate, the State Inspectorate of Protection of Plants and Seeds, the Inspectorate for Trade Quality of Food Produce, as well as to the transfer of several responsibilities of the State Sanitary Inspectorate, the Trade Inspectorate and the Environment Protection Inspectorate – with regard to using and storing of fertilizers – to the new institution, would lead to unification of supervision and monitoring processes. It would also reduce the blurred competence and decision-making responsibilities, ultimately adding to the improvement of food safety in Poland. Considering the results of the audits conducted by the Supreme Audit Office and by the Directorate-General for Health and Food Safety of the European Commission, as well as their own observations, the authors of the article have discussed the justifications for changes in the current food safety system in Poland

Frequency of mutations in PRKN, PINK1, and DJ1 in Patients With Early-Onset Parkinson Disease from neighboring countries in Central Europe

INTRODUCTION: Approximately 10% of patients with Parkinson disease (PD) present with early-onset disease (EOPD), defined as diagnosis before 50 years of age. Genetic factors are known to contribute to EOPD, with most commonly observed mutations in PRKN, PINK1, and DJ1 genes. The aim of our study was to analyze the frequency of PRKN, PINK1, and DJ1 mutations in an EOPD series from 4 neighboring European countries: Czech Republic, Germany, Poland, and Ukraine. METHODS: Diagnosis of PD was made based on UK Brain Bank diagnostic criteria in departments experienced in movement disorders (1 from Czech Republic, 1 from Germany, 9 from Poland, and 3 from Ukraine). EOPD was defined as onset at or before 50 years of age. Of the 541 patients recruited to the study, 11 were Czech, 38 German, 476 Polish, and 16 Ukrainian. All cohorts were fully screened with Sanger sequencing for PRKN, PINK1, and DJ1 and multiplex ligation-dependent probe amplification for exon dosage. RESULTS: PRKN homozygous or double heterozygous mutations were identified in 17 patients: 1 Czech (9.1%), 1 German (2.6%), 14 Polish (2.9%), and 1 Ukrainian (6.3%). PINK1 homozygous mutations were only identified in 3 Polish patients (0.6%). There were no homozygous or compound heterozygous DJ1 mutations in analyzed subpopulations. One novel variant in PRKN was identified in the Ukrainian series. CONCLUSION: In the analyzed cohorts, mutations in the genes PRKN, PINK1, and DJ1 are not frequently observed