22 research outputs found
GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results
Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy
Supplementary material to: Long-term efficacy of T3 analogue Triac in children and adults with MCT8 deficiency: a real-life retrospective cohort study
Bannayan–Riley–Ruvalcaba syndrome with posterior subcapsular congenital cataract and a consensus sequence splicing PTEN mutation
This study, combined with the previously reported
c.634+1G >T mutation [Agrawal et al., 2005] reveal
that exon 6 skipping of PTEN gene produces two
different phenotypes of CS and BRRS associated with
posterior subcapsular congenital cataract. These data
suggest the contribution of other factors that could act downstream of the mutations determining
phenotypic variability [Weng et al., 2001]. In conclusion,
this study expands our knowledge on the
phenotypic variability of BRRS syndrome and
suggests a new mechanism for posterior subcapsular
congenital cataract due to altered function of the
PTEN protein. Further investigations involving a
larger number of patients will be required to confirm
these data
DYT2 screening in early-onset isolated dystonia
Background: Mutations in HPCA, a gene implicated in calcium signaling in the striatum, have been recently described in recessive dystonia cases previously grouped under the term "DYT2 dystonia". Positive patients reported so far show focal onset during childhood with subsequent generalization and a slowly progressive course to adulthood. Methods: 73 patients with isolated dystonia of various distribution, manifesting within 21 years of age, were enrolled in this Italian study and underwent a mutational screening of HPCA gene by means of Sanger sequencing. Results/conclusions: Mean age at onset was 10.2 (+/- 5.1) years and mean age at the time of genetic testing was 33 (+/- 14.2) years. Mean disease duration at the time of enrollment was 22.7 (+/- 12.8) years. None of the patients enrolled was found to carry HPCA mutations, rising suspicion that these probably represent a very rare cause of dystonia in childhood-adolescence. Larger studies will help determining the real mutational frequency of this gene also in different ethnic groups. (C) 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved
La reintroduzione dell'orso bruno (<em>Ursus arctos</em>) sulle Alpi Centrali: definizione e valutazione delle <em>core area</em> degli individui immessi
Per riuscire a salvare il relitto nucleo di orso bruno (<em>Ursus arctos</em>) presente nell'area delle Dolomiti di Brenta da un'estinzione ormai inevitabile, nel 1996 il Parco Naturale Adamello Brenta (Trentino, Italia) ha avviato un progetto che, nell'arco di tempo di quattro anni (1999-2002), ha permesso la liberazione nel territorio trentino di 10 esemplari di orso bruno appartenenti alla popolazione slovena. L'intera operazione ha coinvolto, oltre al Parco (PNAB), la Provincia Autonoma di Trento (PAT) e l'Istituto Nazionale per la Fauna Selvatica (INFS); il progetto è finanziato dall'Unione Europea, attraverso lo strumento finanziario "<em>Life</em> Natura". Gli individui "fondatori" (3 maschi e 7 femmine), secondo quanto stabilito nello Studio di Fattibilità realizzato dall'INFS, rappresentano il numero minimo di esemplari in grado di rendere possibile, nel lungo periodo (>100 anni), la ricostituzione sulle Alpi centrali di una popolazione di orsi vitale ed in grado di autosostenersi. Al momento della cattura ogni soggetto è stato munito di un radiocollare e di due marche auricolari trasmittenti in modo da poterne seguire gli spostamenti nel nuovo ambiente di vita e studiarne il comportamento spaziale. Il presente lavoro mostra i risultati ottenuti dall'elaborazione dei dati derivanti dall'attività di monitoraggio (<em>radio-tracking</em>) svoltasi tra maggio 1999 (prima campagna di catture e rilasci) e giugno 2002 su un campione di 7 esemplari radiocollarati. La prima fase dell'elaborazione dati ha previsto la creazione di un <em>database</em> personalizzato per ogni orso, in cui tutti i dati relativi alle localizzazioni effettuate sono stati ripartiti nelle 4 stagioni - letargo, post-letargo, stagione degli amori, ricerca della tana di svernamento - che caratterizzano il ciclo annuale del plantigrado. Grazie ad un GIS, per ogni orso sono stati calcolati gli <em>home range</em> compresi tra il 100% ed il 20% delle localizzazioni (fix) a disposizione, utilizzando sia il metodo del Minimo Poligono Convesso (MPC) sia il metodo di Kernel. Successivamente è stata elaborata una procedura standard che ha permesso il calcolo, sempre attraverso entrambi i metodi citati, delle <em>core area</em> annuali e stagionali e di individuare nella <em>core area</em> calcolata con Kernel sul 75% delle localizzazioni totali quella in grado di rappresentare al meglio l'uso interno dello spazio da parte dei soggetti studiati. L'analisi della varianza sulle <em>core area</em>, sia annuali sia stagionali, ha evidenziato che gli orsi hanno un comportamento spaziale spiccatamente individuale, che non è possibile generalizzare separando il campione secondo il sesso, l'anno o l'attitudine alla mobilità o sedentarietà mostrate. Dall'analisi delle <em>core area</em> stagionali è emersa una correlazione positiva tra la stagione e l'ampiezza dell'area occupata. Anche se sono necessarie ulteriori indagini statistiche su un set di dati più consistente, il presente lavoro ha concluso che l'alternanza delle stagioni rappresenta sicuramente un fattore in grado di influenzare l'utilizzo del territorio da parte dei soggetti immessi
6.157 A NEW CAUSALITY ALGORITHM TO ENHANCE DIAGNOSIS AND TREATMENT OF CATATONIA DUE TO AUTOIMMUNE CONDITIONS IN CHILDREN AND ADOLESCENTS
Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, inborn error of metabolism characterized by iron accumulation in the basal ganglia and by the presence of dystonia, dysarthria, and retinal degeneration. Mutations in pantothenate kinase 2 (PANK2), the rate-limiting enzyme in mitochondrial coenzyme A biosynthesis, represent the most common genetic cause of this disorder. How mutations in this core metabolic enzyme give rise to such a broad clinical spectrum of pathology remains a mystery. To systematically explore its pathogenesis, we performed global metabolic profiling on plasma from a cohort of 14 genetically defined patients and 18 controls. Notably, lactate is elevated in PKAN patients, suggesting dysfunctional mitochondrial metabolism. As predicted, but never previously reported, pantothenate levels are higher in patients with premature stop mutations in PANK2. Global metabolic profiling and follow-up studies in patient-derived fibroblasts also reveal defects in bile acid conjugation and lipid metabolism, pathways that require coenzyme A. These findings raise a novel therapeutic hypothesis, namely, that dietary fats and bile acid supplements may hold potential as disease-modifying interventions. Our study illustrates the value of metabolic profiling as a tool for systematically exploring the biochemical basis of inherited metabolic diseases. \ua9 2011 Elsevier Inc
Using overlapping VIIRS scenes to observe short term variations in particulate matter in the coastal environment
Expanding the phenotypic spectrum of Allan–Herndon–Dudley syndrome in patients with SLC 16A2 mutations
International audienc