👤 Raphaël Vernet

Food allergy (FA) arises from a complex interplay between an individual's genetic predisposition and environmental factors, and its prevalence is increasing. Genome-wide association studies to date have been hindered by small sample sizes and varying FA definitions. We sought to identify novel FA risk loci by conducting a genome-wide association study meta-analysis in children and adults by using a multiphenotype approach to ensure a good trade-off between sufficient sample size and valid FA definitions. Analyses were conducted separately in children and adults on the basis of the following FA phenotypes: self-report, doctor diagnosis, food-specific sensitization, and doctor diagnosis plus food-specific sensitization. A meta-analysis was performed of genome-wide association studies from up to 16 cohorts of people of European ancestry including 229,426 adults and 14,234 children. Models were adjusted for sex, age, principal components, and, if applicable, further study-specific confounders. Sensitivity models were additionally adjusted for hay fever. Replication was conducted in additional external cohorts and a validation in oral food challenge-defined FA cases. Thirty-seven single nucleotide polymorphisms met suggestive significance (P < 1 × 10 This study identified 37 single nucleotide polymorphisms suggestively associated with FA and demonstrated genetic differences across phenotypes. It highlights the need for a unified FA definition and sheds light on FA's shared genetic architecture with allergies. Show less

The initial saccade of experienced readers tends to land halfway between the beginning and the middle of words, at a position originally referred to as the preferred viewing location (PVL). This study investigated whether a simple physical manipulation-namely, increasing the saliency (brightness or color) of the letter located at the PVL-can positively influence saccadic targeting strategies and optimize reading performance. An eye-movement experiment was conducted with 25 adults and 24 s graders performing a lexical decision task. Results showed that this manipulation had no effect on initial landing positions in proficient readers, who already landed most frequently at the PVL, suggesting that PVL saliency is irrelevant once automatized saccade targeting routines are established. In contrast, the manipulation shifted the peak of the landing site distribution toward the PVL for a cluster of readers with immature saccadic strategies (with low reading-level scores and ILPs close to the beginning of words), but only in the brightness condition, and had a more compelling effect in a cluster with oculomotor instability (with flattened and diffuse landing position curves along with oculomotor and visuo-attentional deficits). These findings suggest that guiding the eyes toward the PVL may offer a novel way to improve reading efficiency, particularly for individuals with oculomotor and visuo-attentional difficulties. Show less

This systematic review aimed to examine the possible implication of visual-perceptual, visuo-attentional and oculomotor processing in the reading deficits frequently experienced by children with Neurofibromatosis type 1 (NF1), as previously shown in dyslexia. Using PRISMA methodological guidelines, we examined 49 studies; most of these reported visual-processing deficits in this population, raising the importance of directly studying the visuo-perceptual and visuo-attentional processes and eye-movement control involved in the learning-to-read process in NF1. The discussion provides a reflection for a better understanding of how visual-processing skills interact with reading deficits in NF1, as well as new avenues for their screening and care. Show less

Mutations in the MYBPC3 gene encoding cardiac myosin-binding protein (cMyBP)-C are frequent causes of hypertrophic cardiomyopathy, but the mechanisms leading from mutations to disease remain elusive. The goal of the present study was therefore to gain insights into the mechanisms controlling the expression of MYBPC3 mutations. We developed a cMyBP-C knock-in mouse carrying a point mutation. The level of total cMyBP-C mRNAs was 50% and 80% lower in heterozygotes and homozygotes, respectively. Surprisingly, the single G>A transition on the last nucleotide of exon 6 resulted in 3 different mutant mRNAs: missense (exchange of G for A), nonsense (exon skipping, frameshift, and premature stop codon) and deletion/insertion (as nonsense but with additional partial retention of downstream intron, restoring of the reading frame, and almost full-length protein). Inhibition of nonsense-mediated mRNA decay in cultured cardiac myocytes or in vivo with emetine or cycloheximide increased the level of nonsense mRNAs severalfold but not of the other mRNAs. By using sequential protein fractionation and a new antibody directed against novel amino acids produced by the frameshift, we showed that inhibition of the proteasome with epoxomicin via osmotic minipumps increased the level of (near) full-length mutants but not of truncated proteins. Homozygotes exhibited myocyte and left ventricular hypertrophy, reduced fractional shortening, and interstitial fibrosis; heterozygotes had no major phenotype. These data reveal (1) an unanticipated complexity of the expression of a single point mutation in the whole animal and (2) the involvement of both nonsense-mediated mRNA decay and the ubiquitin-proteasome system in lowering the level of mutant proteins. Show less