Segregation between SMCHD1 mutation, D4Z4 hypomethylation and Facio-Scapulo-Humeral Dystrophy: a case report

International audienceBackground: The main form of Facio-Scapulo-Humeral muscular Dystrophy is linked to copy number reduction of the 4q D4Z4 macrosatellite (FSHD1). In 5 % of cases, FSHD phenotype appears in the absence of D4Z4 reduction (FSHD2). In 70-80 % of these patients, variants of the SMCHD1 gene segregate with 4qA haplotypes and D4Z4 hypomethylation.Case presentation: We report a family presenting with neuromuscular symptoms reminiscent of FSHD but without D4Z4 copy reduction. We characterized the 4q35 region using molecular combing, searched for mutation in the SMCHD1 gene and determined D4Z4 methylation level by sodium bisulfite sequencing. We further investigated the impact of the SMCHD1 mutation at the protein level and on the NMD-dependent degradation of transcript. In muscle, we observe moderate but significant reduction in D4Z4 methylation, not correlated with DUX4-fl expression. Exome sequencing revealed a heterozygous insertion of 7 bp in exon 37 of the SMCHD1 gene producing a loss of frame with premature stop codon 4 amino acids after the insertion (c.4614-4615insTATAATA). Both wild-type and mutated transcripts are detected.Conclusion: The truncated protein is absent and the full-length protein level is similar in patients and controls indicating that in this family, FSHD is not associated with SMCHD1 haploinsufficiency

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Langage et interaction dans une situation conversationnelle médiatisée : les messageries conviviales du minitel

We intended to apply the linguistic and psycho-sociological approaches to the study of a corpus of electronic mail conversations conveyed by "minitel" (collected thanks to confederates). From the linguistic point of view, the language used on "minitel" is characterized as written utterances simulating spoken utterances and we bring some linguistic evidence in support of that hypothesis. From the psycho-sociological point of view, we try to enlighten the relational dimension of such conversations the partners of which are located in a somewhat unreal space. We'll try to grasp how relations are established (studying in particular the initial sequences of conversations) and to apprehend their specificity.Partant d'un corpus de conversations recueillies sur une messagerie conviviale du minitel par l'intermédiaire de "compères", nous avons cherché à mêler deux approches : linguistique et psychosociologique. L'analyse linguistique s'attachera à caractériser le langage employé sur minitel (un écrit produisant un effet d'oral) puis elle tentera d'isoler quelques uns des procédés qui confirmeraient cette hypothèse. L'approche psychosociologique, elle, a pour but d'éclairer la dimension relationnelle des conversations dont les acteurs, tels des personnages masqués, évoluent dans un espace quelque peu imaginaire. Nous chercherons à comprendre comment des relations se nouent (notamment en étudiant les séquences d'ouverture) et ce qu'elles ont de spécifique.Lévy Emmanuelle. Langage et interaction dans une situation conversationnelle médiatisée : les messageries conviviales du minitel. In: Linx, n°28, 1993. Sans thème, sous la direction de Jacques Anis et Eliane Koskas. pp. 69-84

Quentin Skinner: “Concepts only have histories”.

Emmanuelle Tricoire (ET) : What about your field? What is your field? QS: Well that is, immediately, a difficult question. I was for nearly twenty years the Professor of Political Science at Cambridge, but my present Chair is in the Faculty of History. My official title is Regius Professor of Modern History. I suppose that, by formation and existentially, I am a historian, definitely, rather than anything else. But obviously, I have studied philosophy as well, and I have taught both ..

Diagnostic yield of repeat genetic testing in idiopathic chronic pancreatitis

International audienceGenetic testing is performed for unexplained pancreatitis. The aim of this study was to evaluate the diagnostic value of repeating genetic testing in idiopathic pancreatitis when new predisposing genes are identified. We investigated 330 patients who were initially screened for PRSS1, SPINK1 and CFTR genes. A new analysis was performed by Next-Generation Sequencing (NGS) for PRSS1, SPINK1, CFTR, CTRC, CASR, CPA1, TRPV6 genes and the CEL-HYB1 allele in clinical practice, and patients were included in our cohort study. Additional rare variants were identified in 7.3 % of the patients. Screening for new pancreatitis genes is recommended when initial screening is limited. Routine use of NGS is a useful diagnostic tool in these cases

Sequential design of experiments for parameter estimation with application to numerical dosimetr

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Retours en Emilia : de la recherche-action à la création de communautés vivantes et apprenantes

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