The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development

A single nucleotide polymorphism causing constitutive activation of Vav1 results in increased natural Treg generation and is responsible for the imbalance between Vav1 GEF and adaptor functions

Allergic contact dermatitis to diclofenac gel due to propylene glycol sensitization: usefulness of repeated open application tests to determine safer alternatives

Topical non-steroidal anti-inflammatory drugs (NSAIDs) can cause allergic contact dermatitis (ACD) and photocontact dermatitis. Although topical diclofenac is associated with fewer side effects than other topical NSAIDs, rare cases of contact dermatitis have been reported

Extending the prenatal Noonan's phenotype by review of ultrasound and autopsy data

Abstract Objectives The antenatal phenotypic spectrum of Noonan Syndrome (NS) requires better characterization. Methods This multicenter retrospective observational included 16 fetuses with molecularly confirmed NS admitted for fetopathological examination between 2009 and 2016. Results Among 12 pathogenic variants (PV) in PTPN11 (80%), 5 (42%) fell between position c.179 and c.182. Ultrasound showed increased nuchal translucency ( n = 13/16, 93%), increased nuchal fold after 15 weeks of gestation ( n = 12/16, 75%), pleural effusions ( n = 11/16, 69%), polyhydramnios ( n = 9/16, 56%), hydrops ( n = 7/16, 44%), cardiovascular ( n = 6/16, 38%) and cerebral ( n = 4/16, 25%) anomalies. Fetopathological examination found dysmorphic features in all cases, cardiovascular anomalies ( n = 12/15, 80%), pulmonary hypoplasia ( n = 10/15, 67%), effusions ( n = 7/15, 47%) and neuropathological anomalies ( n = 5/15, 33%). Hydrops was significantly ( p = 0.02) more frequent in the four fetuses with RIT1 , NRAS and RAF1 PV versus the 12 fetuses with PTPN11 PV. Conclusions Increased nuchal translucency and nuchal fold is common in NS. Noonan Syndrome antenatal phenotype showed high in utero fetal death, hydrops, prenatal pleural effusion and pulmonary hypoplasia, although the inclusion of only deceased fetuses will have selected more severe phenotypes. Non‐specific cardiovascular and neurological abnormalities should be added to NS antenatal phenotype. Next generation sequencing will help detect more genotypes, clarifying the prenatal phenotype and identifying genotype‐phenotype correlations

Terminal 6q deletions cause brain malformations, a phenotype mimicking heterozygous DLL1 pathogenic variants : A multicenter retrospective case series

International audienceTerminal 6q deletion is a rare genetic condition associated with a neurodevelopmental disorder characterized by intellectual disability and structural brain anomalies. Interestingly, a similar phenotype is observed in patients harboring pathogenic variants in the DLL1 gene. Our study aimed to further characterize the prenatal phenotype of this syndrome as well as to attempt to establish phenotype-genotype correlations. We collected ultrasound findings from 22 fetuses diagnosed with a pure 6qter deletion. We reviewed the literature and compared our 22 cases with 14 fetuses previously reported as well as with patients with heterozygous DLL1 pathogenic variants. Brain structural alterations were observed in all fetuses. The most common findings (>70%) were cerebellar hypoplasia, ventriculomegaly, and corpus callosum abnormalities. Gyration abnormalities were observed in 46% of cases. Occasional findings included cerebral heterotopia, aqueductal stenosis, vertebral malformations, dysmorphic features, and kidney abnormalities. This is the first series of fetuses diagnosed with pure terminal 6q deletion. Based on our findings, we emphasize the prenatal sonographic anomalies, which may suggest the syndrome. Furthermore, this study highlights the importance of chromosomal microarray analysis to search for submicroscopic deletions of the 6q27 region involving the DLL1 gene in fetuses with these malformations

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed