16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Wine-Gauging at Damme [The evidence of a late medieval manuscript]

Abstract. During the late Middle Ages, Damme, the outport of Bruges, was an important staple town, i.a. for wines. The measurement of the volume of the barrels for tax and excise purposes was farmed out to the Hospital of St. John. Although the practice of measuring wine barrels was performed throughout the Middle Ages, few medieval documents about how this was done are known. The history of Damme shows that gauging was performed in the Low Countries as well as in France during this period, thereby undermining the assertion that the gauging rod is a Southern German invention. It will be shown that the manuscript which is presented here is one of the oldest in which the construction of the gauging rod is explained. The way in which this was done is very peculiar. Also on the back of the manuscript are some monastic ciphers; in this notation every number is written as a single cipher.Résumé. Jauger les tonneaux de vin dans le port de Damme. Le témoignage d'un manuscrit de la fin de l'époque médiévale. À la fin du Moyen Âge, Damme, Г avant-port de Bruges, était une importante ville d'étape, en particulier pour le commerce des vins. La mesure du volume des tonneaux était effectuée à des fins fiscales et était affermée à l'Hôpital Saint John. Quoique le jaugeage du vin fût courant tout au long du Moyen Âge, il subsiste peu de documents qui permettent de savoir de quelle manière il était pratiqué. L'histoire de Damme montre que cette technique était malgré tout employée aux Pays-Bas aussi bien qu'en France pendant toute cette période, détruisant par là l'assertion selon laquelle les instruments de jauge étaient une invention de l'Allemagne du Sud. On montrera que le manuscrit ici présenté est l'un des plus anciens dans lesquels la méthode de jauge soit explicitée et que la méthode utilisée était très particulière. En outre, au verso du manuscrit, se trouvent des nombres de type monastique qui correspondent à un système de notation original dans lequel chaque chiffre est figuré par un signe spécifique.Meskens Ad, Bonte Germain, Groot Jacques de, Jonghe Mieke de, King David A. Wine-Gauging at Damme [The evidence of a late medieval manuscript]. In: Histoire & Mesure, 1999 volume 14 - n°1-2. Varia. pp. 51-77

Inactivation of Murine Norovirus-1, Coliphage phi X174 and Bacillus Phage B40-8 on Surfaces and Fresh-Cut iceberg Lettuce by Hydrogen Peroxide and UV Light

In this study, the inactivating properties of liquid hydrogen peroxide (L-H2O2), vaporized hydrogen peroxide (V-H2O2), UV light, and a combination of V-H2O2 and UV light were tested on murine norovirus 1 (MNV-1) and bacteriophages (X174 and B40-8) as models for human noroviruses. Disinfection of surfaces was examined on stainless steel discs based on European Standard EN 13697 (2001). For fresh-produce decontamination, a mixture of the viruses was inoculated onto shredded iceberg lettuce and treated after overnight incubation at 2°C. According to our results, L-H2O2 (2.1%) was able to inactivate MNV-1 and X174 on stainless steel discs by approximately 4 log10 units within 10 min of exposure, whereas for B40-8, 15% of L-H2O2 was needed to obtain a similar reduction in 10 min. Only a marginal reduction (≤1 log10 unit after 5 min of exposure) by V-H2O2 (2.52%) was achieved for the tested model viruses, although in combination with UV light, a 4-log10-unit decrease within 5 min of treatment was observed on stainless steel discs. Similar trends were observed for the decontamination of shredded iceberg lettuce, but the viral decline was reduced. These results demonstrated that both L-H2O2 and a combination of V-H2O2 and UV light can be used for norovirus inactivation on surfaces; V-H2O2 (2.52%) in combination with UV light is promising for decontamination of fresh produce with much less consumption of water and disinfectant.status: publishe

Inactivation of Murine Norovirus 1, Coliphage φX174, and Bacteroides fragilis Phage B40-8 on Surfaces and Fresh-Cut Iceberg Lettuce by Hydrogen Peroxide and UV Light

In this study, the inactivating properties of liquid hydrogen peroxide (L-H2O2), vaporized hydrogen peroxide (V-H2O2), UV-light and a combination of V-H2O2 and UV-light were tested on murine norovirus 1 (MNV-1), bacteriophages (φX174 and B40-8) as models for human noroviruses. Disinfection of surfaces was examined on stainless steel discs based on EN 13697 : 2001 (12). For the fresh produce decontamination, a mixture of the viruses was inoculated onto shredded iceberg lettuce and treated after overnight incubation at 2°C. According to our results, L-H2O2 [2.1%] was able to inactivate MNV-1 and φX174 on stainless steel discs by approximately 4-log10 within 10 min exposure, whereas for B40-8 15% of L-H2O2 was needed to get a similar reduction in 10 min. Only a marginal reduction (≤1-log10, 5 min exposure) by V-H2O2 [2.52%] was achieved for the tested model viruses. Although in combination with UV-light, a 4-log10 decrease within 5 min treatment was observed on stainless steel discs. Similar trends were obtained for the decontamination of shredded iceberg lettuce but the viral decline was reduced. These results demonstrated that both L-H2O2 and combination of V-H2O2 and UV-light can be used for norovirus inactivation on surfaces; V-H2O2 [2.52%] in combination with UV-light is promising as a decontamination of fresh produce with much less consumption of water and disinfectant