The KIT gene in familial mastocytosis

Familial cutaneous mastocytosis is an exceptional condition of unknown etiology. In this study we report the largest series of patients with familial cutaneous mastocytosis without other manifestations (18 affected subjects from seven unrelated families), and we investigate the role of germ-line KIT mutations in the pathogenesis of the disease. The mean age at onset was 5.4 years (range from birth to 22 years), and the clinical behavior was variable over a mean follow up period of 15.1 years (range 2-36): improvement in seven, stability in eight and worsening in the remaining three patients. The pattern of inheritance was compatible with an autosomal dominant trait with incomplete penetrance; a female preponderance (14 females vs 4 males, ratio 3.5:1) was noted; among the six women who have been pregnant at least once, three experienced important clinical changes during pregnancy. No germ-line mutation was found in the exons 10, 11, and 17 of the KIT proto-oncogene, which are the most commonly mutated exons in sporadic mastocytosis. However, in the majority of affected subjects we found the Met541Leu polymorphic variant of the KIT gene, which seems to confer a growth advantage to mast cells in vitro. This observation further suggests that the Met541Leu may be a predisposing factor of cutaneous mastocytosis, although it seems to be neither necessary nor sufficient for the development of the disease.

Variety, flexibility, and use of abstract concepts. A multiple grounded perspective.

The nature of concepts is a matter of intense debate in cognitive sciences. While traditional views claim that conceptual knowledge is represented in a unitary symbolic system, recent Embodied and Grounded Cognition theories (EGC) submit the idea that conceptual system is couched in our body and influenced by the environment (Barsalou, 2008). One of the major challenges for EGC is constituted by abstract concepts (ACs), like fantasy. Recently, some EGC proposals addressed this criticism, arguing that the ACs comprise multifaced exemplars that rely on different grounding sources beyond sensorimotor one, including interoception, emotions, language, and sociality (Borghi et al., 2018). However, little is known about how ACs representation varies as a function of life experiences and their use in communication. The theoretical arguments and empirical studies comprised in this dissertation aim to provide evidence on multiple grounding of ACs taking into account their varieties and flexibility. Study I analyzed multiple ratings on a large sample of ACs and identified four distinct subclusters. Study II validated this classification with an interference paradigm involving motor/manual, interoceptive, and linguistic systems during a difficulty rating task. Results confirm that different grounding sources are activated depending on ACs kind. Study III-IV investigate the variability of institutional concepts, showing that the higher the law expertise level, the stronger the concrete/emotional determinants in their representation. Study V introduced a novel interactive task in which abstract and concrete sentences serve as cues to simulate conversation. Analysis of language production revealed that the uncertainty and interactive exchanges increase with abstractness, leading to generating more questions/requests for clarifications with abstract than concrete sentences. Overall, results confirm that ACs are multidimensional, heterogeneous, and flexible constructs and that social and linguistic interactions are crucial to shaping their meanings. Investigating ACs in real-time dialogues may be a promising direction for future research.