The Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal (CLOVES) syndrome is a genetic disorder due to a gain of function mutation of the PIK3CA in a mosaic fashion. This rare condition is associated with severe deformation and poor survival. We identified a new drug able to dramatically improve the outcome of patients with this rare disease. The purpose of the Proof of Concept grant is to better understand the molecular effect of this drug and to rapidly accede to Orphan drug designation.

Spelling in French raises recurring problems and several studies show that such difficulties, specifically misspellings, can pose a major handicap to career achievement. Studies on spelling difficulties and the way to overcome them remain rare, particularly in comparison to studies on reading, both in French and in other writing systems. While some studies on reading acquisition contribute to our knowledge of spelling development, studies specifically on spelling acquisition are indispensable. Despite the high correlation between performance on reading and spelling tasks, there are often children or adults who are good readers but poor spellers, whereas the reverse pattern is far more rare, and perhaps nonexistent (according to some researchers). This discrepancy between reading and spelling performance can be explained by differences in cognitive demands: a word can often be read based on partial cues, but each individual letter in a word has to be produced in spelling. In addition to this difference, which is found across all writing systems, there are two particular challenges in French: 1) the relationship between oral and written units is far more irregular in the conversion from oral to written language than from writing to speech; 2) silent letters are frequent. - The first aim of this project is to specify how different types of information are used in the course of spelling acquisition. The second aim is to determine empirically the impact of specific educational practices on spelling acquisition. - The first set of studies will specify how different types of information (phonological, orthographic, morphological) are used during spelling acquisition by elementary school children (grades 1 to 5). We will determine the aspects of the orthography that pose particular difficulties to children with various performance profiles: good in both reading and spelling; poor in both reading and spelling; good readers who are poor in spelling; good spellers who are poor readers (should this group exist). While studies to date have mainly focused on the role of phonology and word specific knowledge, we will extend beyond this scope to explore the impact of knowledge of orthographic and morphological regularities. We will consider specifically the integration of these two different sources of information, which, to date, have been studied independently. Corpus analyses will allow us to characterize the nature, origins and evolution of misspellings, as well as to describe their relationship with various performance profiles. Experimental studies will permit us to address questions to which corpus analyses cannot provide complete answers. The same children will be given both standardized and experimental tasks. These tasks will allow us to assess children's knowledge of orthographic regularities and their morphological knowledge. We will also analyze children's eye movement during reading in order to explore whether differences in the way children process words in the reading task are associated with differences in spelling performance. - A second series of studies will explore the impact of specific educational practices on spelling acquisition. In particular, we are interested in the role of mistakes in children's learning. This is an important question because many pedagogical approaches involve exposure to and/or production of errors (e.g., the choice between two spellings, one correct, and one incorrect, especially in educational software). We will aim to specify the conditions under which such experiences with errors are beneficial or, on the contrary, detrimental to the learning process. We will assess the efficacy of various modes of attentional processing in situations in which learners are exposed (or not) to specific types of errors (learning the spelling of a word through reading it vs. copying it vs. choosing between two spellings, one correct, the other incorrect). We will assess whether the impact of mistakes varies as a...