Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Stato e politica in Alfredo Rocco

Dottorato di ricerca in storia del pensiero politico e delle istituzioni politiche. 6. ciclo. Tutore A. Colombo. Cotutore G. GozziConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Un'ambiguità istituzionale: il Gran Consiglio Nazionale del fascismo (1923-1928). Problemi e prospettive storiografiche

Un'ambiguit&agrave; istituzionale: il Gran Consiglio Nazionale del fascismo (1923-1928). Problemi e prospettive storiografich

Ricordo di Ernesto Molinari

Ricordo di Ernesto Molinar

Il ruolo della ricerca accademica sule mafie fra comunità universitaria, istituzioni e società

i due curatori del volume con Rocco Sciarrone, sociologo, e Alberto Vannucci (scienziato della politica) condividono alcune conclusioni, anche di natura prospettica, sul ruolo dell'università in tema di mafie

The role of academic research on mafias amid the academic community institutions and society

Quattro docenti universitari di discipline diverse - i due curatori del volume (un giurista e un ingegnere), un sociologo e uno scienziato della politica - si soffermano sul ruolo dell'università, in quanto comunità epistemica, che associa la condivisione di un insieme di credenze valoriali e principi normativi all’istanza di una potenziale applicazione in chiave di riforma delle conoscenze prodotte. Tra gli aspetti su cui ci si sofferma vi è l'impegno accademico nei temi delle mafie e della legalità attraverso le tre missioni in quanto espressione di un'istituzione di alta cultura con specifica collocazione nel quadro costituzionale. Tale contributo traccia un nuovo percorso che gli studiosi e gli atenei possono realizzare nella prospettiva della creazione di una forma associative che ricomprenda tutti gli studiosi della materia, in grado di interfacciassi con gli attori dell'antimafia istituzionale e sociale

Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome

Background Neurofilament light chain (NfL) represents a promising biomarker for axonal injury. We present the first exploratory study on serum NfL in patients with a clinically isolated syndrome (CIS) and healthy controls