Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: towards recommendation for molecular testing and management

International audienceSHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended

Utilisation de l'interferon alpha dans un cas d'hémangiome hépatique chez un nourrisson

ROUEN-BU Médecine-Pharmacie (765402102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Dietary treatment of colic caused by excess gas in infants: Biochemical evidence

AIM: To evaluate the impact of feeding colicky infants with an adapted formula on the hydrogen breath test and clinical symptoms

Intoxication accidentelle à l'arsenic par une pierre de collection

L'objectif de ce travail est de présenter un cas d'intoxication à l'arsenic par une pierre de collection et de proposer des mesures pour éviter ce type d'accident. L'observation que nous rapportons concerne un nourrisson de 17 mois qui joue avec les pierres de collection de son frère aîné. Celles-ci font partie d'un assortiment de pierres que l'on peut se procurer dans les magasins de souvenirs ou sur les marchés, sans qu 'aucune mention ne soit faite de leur dangerosité éventuelle. Le jeune Flavian est surpris par sa mère avec des pierres dans la bouche. La mère le fait cracher et élimine le maximum de particules puis lui rince la cavité buccale à l'eau. Elle se rend aux Urgences Pédiatriques, l'enfant ne présente pas de symptomatologie clinique particulière. Les pierres, de couleur jaune vif sont identifiées comme étant de l'orpiment ou sulfure naturel d'arsenic (As2S3). Le dosage de l'arsenic (As) est réalisé par spectrométrie d'absorption atomique électrothermique au four graphite, équipé d'un dispositif Zeeman pour la correction du bruit de fond (Spectra AA 800 avec GTA 100 Varian). La méthode des ajouts dosés que nous utilisons a été mise au point et validée au laboratoire selon les critères usuels. Le dosage spécifique de l'As inorganique, la seule forme d'As toxique, est effectué après extraction par le chloroforme. L'As urinaire inorganique, montre une élévation très importante du rapport urinaire As/créatinine à 327 µg/g (sujet exposé < 50 µg/g en fin de semaine de travail). Un contrôle de l'As sanguin et urinaire réalisé trois mois plus tard s'avère normal. Cette observation pose un réel problème de santé publique : minerais en vente libre, sans aucune mention, qui plus est destinés aux enfants alors qu 'il s'agit de divers sels de métaux dont la toxicité peut être redoutable. Nous proposons un étiquetage adapté mentionnant la dangerosité éventuelle du minerai et l'emploi d'emballages inviolables pour les minéraux toxiques

PIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy

International audienceShort stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome is a developmental disorder with an unknown genetic cause and hallmarks that include insulin resistance and lack of subcutaneous fat. We ascertained two unrelated individuals with SHORT syndrome, hypothesized that the observed phenotype was most likely due to de novo mutations in the same gene, and performed whole-exome sequencing in the two probands and their unaffected parents. We then confirmed our initial observations in four other subjects with SHORT syndrome from three families, as well as 14 unrelated subjects presenting with syndromic insulin resistance and/or generalized lipoatrophy associated with dysmorphic features and growth retardation. Overall, we identified in nine affected individuals from eight families de novo or inherited PIK3R1 mutations, including a mutational hotspot (c.1945C>T [p.Arg649Trp]) present in four families. PIK3R1 encodes the p85 alpha, p55 alpha, and p50 alpha regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play a key role in insulin signaling. Functional data from fibroblasts derived from individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling. Our findings extend the genetic causes of severe insulin-resistance syndromes and provide important information with respect to the function of PIK3R1 in normal development and its role in human diseases, including growth delay, Rieger anomaly and other ocular affections, insulin resistance, diabetes, paucity of fat, and ovarian cysts

Measurements and controls implementation for WEST

The WEST platform consists in a major upgrade of Tore Supra towards a steady-state tungsten (W) diverted tokamak. In support of this, significant developments are performed on the measurement systems (diagnostics); the control, data access and communication (CODAC); the plasma control system (PCS), the monitoring and protection of the first wall and modelling to prepare the restart of the plasma. Thanks to collaboration agreements already in force, most of the developments and some hardware procurements are performed with the help of several international partners. This paper discusses the present status of developments regarding the measurements and control for the WEST project. In particular, the integration of about 50 diagnostics in ports is completed, and their in-vessel and ex-vessel installation is underway. The refurbishment of the CODAC network architecture has been completed. The development of the new acquisition units based on PXI and of the Plasma Control System (PCS) is ongoing and some units are already available. In parallel, to prepare the plasma restart, the development of plasma magnetic and kinetic controllers has been performed on simplified plant and actuator models and plasma models

Dissertatio historica de initiis monarchiae Babyloniorum, quam, cum cons. ampliss. Colleg. Philos. in Reg. Acad. Upsal. sub praesidio ... Jacobi Arrhenii ... publico examini modeste subjicit Petrus Hagberg Gestr. In audit. Gustav. maj. ad d. 25. Maji. Anni MDCCV.

International audienceBackground : The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedlybecause of changing environmental factors, which are yet largely unknown. The purpose of the study was tounravel environmental markers associated with T1D. Methods : Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends ofthe patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis.The analysis took into account the matching between cases and controls. A second analysis used propensity scoremethods. Results : We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnutcocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a petby old age. Conclusions : The found statistical association of new environmental markers with T1D calls for replication in othercohorts and investigation of new environmental areas

Additional file 1: of Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

The questionnaire used in the current study. (PDF 620 kb