A 7-year-old boy and a 14-year-old girl initially diagnosed with toxic shock syndrome and tested positive for sars-cov-2 infection, supporting a diagnosis of multisystem inflammatory syndrome in children (Mis-c)

Background: Multisystem inflammatory syndrome in children (MIS-C) has recently been described in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This report describes 2 children with MIS-C who were initially diagnosed with toxic shock syndrome but who tested positive for SARS-CoV-2 infection on reverse transcription-polymerase chain reaction, supporting the diagnosis of MIS-C. Case Reports: Case 1. A 7-year-old boy with fever, cough, and dyspnea was treated with oxygen, intravenous immunoglobulin (IVIG) infusion, and methylprednisolone and showed a worsening of clinical conditions, persistent fever, hypotension, and hematological parameters compatible with macrophage activation syndrome (MAS). Three intravenous boluses of methylprednisolone (30 mg/kg/day) were followed by a progressive resolution. Case 2. A 14-year-old girl with syncope, fever, diarrhea, oliguria, and increased creatinine levels required fluid infusion and correction of electrolyte imbalance. The increase of creatine phosphokinase (CPK), myoglobin, troponin, and creatine kinase-MB (CK-MB) was associated with grade I atrioventricular block and pericardial effusion. The patient showed myositis and severe muscular weakness, with hematological parameters compatible with MIS-C. She started IVIG and 3 intravenous boluses of methylprednisolone. However, bradycardia, tachypnea, severe hypotension, loss of consciousness, oliguria, bilateral ground-glass pneumonia, bilateral pleural, and peritoneal effusion, in the absence of thromboembolism, required treatment with furosemide, albumin, and enoxaparin, and was followed by a prompt resolution. Conclusions: These 2 pediatric cases highlight the importance of SARS-CoV-2 testing in all patients with acute symptoms and signs of infection during the COVID-19 pandemic. As new variants of SARS-CoV-2 emerge, cases of MIS-C can become more prevalent, and pediatricians should be aware of diagnostic and management guidelines

Unique resistance traits against downy mildew from the center of origin of grapevine (Vitis vinifera)

The Eurasian grapevine (Vitis vinifera), an Old World species now cultivated worldwide for high-quality wine production, is extremely susceptible to the agent of downy mildew, Plasmopara viticola. The cultivation of resistant V. vinifera varieties would be a sustainable way to reduce the damage caused by the pathogen and the impact of disease management, which involves the economic, health and environmental costs of frequent fungicide application. We report the finding of unique downy mildew resistance traits in a winemaking cultivar from the domestication center of V. vinifera, and characterize the expression of a range of genes associated with the resistance mechanism. Based on comparative experimental inoculations, confocal microscopy and transcriptomics analyses, our study shows that V. vinifera cv. Mgaloblishvili, native to Georgia (South Caucasus), exhibits unique resistance traits against P. viticola. Its defense response, leading to a limitation of P. viticola growth and sporulation, is determined by the overexpression of genes related to pathogen recognition, the ethylene signaling pathway, synthesis of antimicrobial compounds and enzymes, and the development of structural barriers. The unique resistant traits found in Mgaloblishvili highlight the presence of a rare defense system in V. vinifera against P. viticola which promises fresh opportunities for grapevine genetic improvemen

Complex segmental duplications mediate a recurrent dup(X)(p11.22- p11.23) associated with mental retardation, speech delay and EEG anomalies in males and females

Submicroscopic copy-number variations make a considerable contribution to the genetic etiology of human disease.We have analyzed subjects with idiopathic mental retardation (MR) by using whole-genome oligonucleotide-based array comparative genomic hybridization (aCGH) and identified familial and de novo recurrent Xp11.22-p11.23 duplications in males and females with MR, speech delay, and a peculiar electroencephalographic (EEG) pattern in childhood. The size of the duplications ranges from 0.8–9.2 Mb. Most affected females show preferential activation of the duplicated X chromosome. Carriers of the smallest duplication show X-linked recessive inheritance. All other affected individuals present dominant expression and comparable clinical phenotypes irrespective of sex, duplication size, and X-inactivation pattern. The majority of the rearrangements are mediated by recombination between flanking complex segmental duplications. The identification of common clinical features, including the typical EEG pattern, predisposing genomic structure, and peculiar X-inactivation pattern, suggests that duplication of Xp11.22-p11.23 constitutes a previously undescribed syndrome

The Koolen-de Vries syndrome: A phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

Genetics of disease, diagnosis and treatmen