Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller’s dementia infantilis, a rare subtype of autism spectrum disorder

International audienceAbstractBackgroundDeletions and mutations involving the SHANK3 gene lead to a nonspecific clinical presentation with moderate to profound intellectual disability, severely delayed or absent speech, and autism spectrum disorders (ASD).Better knowledge of the clinical spectrum of SHANK3 haploinsufficiency is useful to facilitate clinical care monitoring and to guide molecular diagnosis, essential for genetic counselling.Case presentationHere, we report a detailed clinical description of a 10-year-old girl carrying a pathogenic interstitial 22q13.3 deletion encompassing only the first 17 exons of SHANK3.The clinical features displayed by the girl strongly suggested the diagnosis of dementia infantilis, described by Heller in 1908, also known as childhood disintegrative disorder.ConclusionOur present case confirms several observations according to which regression may be part of the clinical phenotype of SHANK3 haploinsufficiency. Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years

Proposal, project, practice, pause: developing a framework for evaluating smart domestic product engagement

Smart homes are fast becoming a reality, with smart TVs, smart meters and other such “smart” devices/systems already representing a substantial household presence. These, which we collectively term “smart domestic products” (SDPs), will need to be promoted, adopted, and normalized into daily routines. Despite this, the marketing canon lacks a substantive discourse on pertinent research. We look to help correct this by melding ideas from organizational sociology, innovation diffusion and appropriation studies, and service dominant logic. Consequently, we suggest a framework for research that responds directly to the specific characteristics of SDPs. Using the SDP eco-system as a context, our framework emphasizes the interplay of embeddedness, practice, value and engagement. It comprises a four-stage horizontal/ longitudinal axis we describe as proposal, project, practice and pause. Cross-sectionally we focus on value, and combine aspects of existing thought to suggest how this impacts each stage of our engagement continuum. We subsequently identify perceived personal advantage as the resultant of these two axes and propose this as the key for understanding consumer and SDP sociomaterial engagement. This article also advances a definition of SDPs and ends with an agenda for further research

Dendritic overgrowth and elevated ERK signaling during neonatal development in a mouse model of autism

Autism spectrum disorder (hereafter referred to as "ASD") is a heterogeneous neurodevelopmental condition characterized by impaired social communication and interactions, and restricted, repetitive activities or interests. Alterations in network connectivity and memory function are frequently observed in autism patients, often involving the hippocampus. However, specific changes during early brain development leading to disrupted functioning remain largely unclear. Here, we investigated the development of dendritic arbor of hippocampal CA1 pyramidal neurons in the BTBR T+tf/J (BTBR) mouse model of autism. BTBR mice display the defining behavioural features of autism, and also exhibit impaired learning and memory. We found that compared to control C57BL/6J (B6) animals, the lengths of both apical and basal dendrites were significantly greater in neonatal BTBR animals. Further, basal dendrites in the BTBR mice had higher branching complexity. In contrast, cross-sectional area of the soma was unchanged. In addition, we observed a similar density of CA1 pyramidal neurons and thickness of the neuronal layer between the two strains. Thus, there was a specific, compartmentalized overgrowth of dendrites during early development in the BTBR animals. Biochemical analysis further showed that the extracellular signal-regulated kinases (ERK) pathway was up-regulated in the hippocampus of neonatal BTBR animals. Since dendritic structure is critical for information integration and relay, our data suggest that altered development of dendrites could potentially contribute to impaired hippocampal function and behavior observed in the BTBR model, and that this might be related to increased activation of the ERK pathway