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The "22q11.2 duplication" is a variably penetrant copy number variant (CNV) associated with a broad spectrum of clinical manifestations including autism spectrum disorders (ASD), and epilepsy. Here, we report on pathogenic "HUWE1" and "KIF1A" mutations in two severely affected ASD/ID participants carrying a 22q11.2 duplication. Based on previous studies, this CNV was originally considered as disease-causing. Yet, owing to their clinical severity, the participants were further investigated by next generation sequencing and eventually found to carry pathogenic mutations in "HUWE1" and "KIF1A" respectively. We suggest giving consideration to additive effect of 22q11.2 duplication and pathogenic mutations when clinical presentation is either unusually severe or associated with atypical features. Caution should be exercised when delivering genetic counseling for variably penetrant CNVs, as uncertain penetrance of this CNV may lead to ignore additive pathogenic mutations. Systematic panel or exome sequencing of known ASD genes should be recommended when counseling families of patients carrying variably penetrant CNV.

Dans cette étude de corpus, on aborde la question du comportement dialogique de soutien en entretien clinique avec le patient souffrant de schizophrénie. Nous partons de l’analyse des interactions langagières, en présupposant que le cadre spécifique de l’interaction verbale de type clinique est un lieu d’expression privilégié de “comportement dialogique de soutien”. Sur la base d’une exploration empirique, nous proposons l’élaboration d’un modèle interlocutoire dynamique de ce que l’on pourrait interpréter comme une forme d’écoute attentive, de soutien, en nous basant notamment sur des indicateurs lexicaux particuliers que sont les backchannels. Nous décrivons les différents types d’organisation discursive au sein desquelles les interlocuteurs adoptent un comportement de soutien manifeste. Nous extrayons les propriétés des configurations discursives au sein desquelles le comportement de soutien de l’un des interlocuteurs (la psychologue, par exemple) a pour effet d’amener le locuteur (le patient, par exemple) à modifier sa stratégie argumentative. Les analyses empiriques portent sur la totalité du temps d'enregistrement de 10 entretiens réalisés avec des personnes souffrant de schizophrénie (recueillis en hôpital psychiatrique) et 10 entretiens réalisés avec des sujets témoins.

The 22q11.2 duplication is a variably penetrant copy number variant (CNV) associated with a broad spectrum of clinical manifestations including autism spectrum disorders (ASD), and epilepsy. Here, we report on pathogenic HUWE1 and KIF1A mutations in two severely affected ASD/ID participants carrying a 22q11.2 duplication. Based on previous studies, this CNV was originally considered as disease-causing. Yet, owing to their clinical severity, the participants were further investigated by next generation sequencing and eventually found to carry pathogenic mutations in HUWE1 and KIF1A respectively. We suggest giving consideration to additive effect of 22q11.2 duplication and pathogenic mutations when clinical presentation is either unusually severe or associated with atypical features. Caution should be exercised when delivering genetic counseling for variably penetrant CNVs, as uncertain penetrance of this CNV may lead to ignore additive pathogenic mutations. Systematic panel or exome sequencing of known ASD genes should be recommended when counseling families of patients carrying variably penetrant CNV., Author(s): Caroline Demily [sup.1] , Gaétan Lesca [sup.2] [sup.3] , Alice Poisson [sup.1] , Marianne Till [sup.2] , Giulia Barcia [sup.4] , Nicolas Chatron [sup.2] [sup.3] , Damien Sanlaville [sup.2] [...]

Background: While adult outcome in autism spectrum disorder (ASD) is generally measured using socially valued roles, it could also be understood in terms of aspects related to health status – an approach that could inform on potential gender differences. Methods: We investigated gender differences in two aspects of outcome related to health-status, i.e. general functioning and self-perceived health status, and co-occurring health conditions in a large multi-center sample of autistic adults. Three hundred and eighty-three participants were consecutively recruited from the FondaMental Advanced Centers of Expertise for ASD cohort (a French network of seven expert centers) between 2013 and 2020. Evaluation included a medical interview, standardized scales for autism diagnosis, clinical and functional outcomes, self-perceived health status and verbal ability. Psychosocial function was measured using the Global Assessment of Functioning scale. Results: While autistic women in this study were more likely than men to have socially valued roles, female gender was associated with poorer physical and mental health (e.g. a 7-fold risk for having three or more co-occurring physical health conditions) and a poorer self-perceived health status. Psychosocial function was negatively associated with depression and impairment in social communication. Half of the sample had multiple co-occurring health conditions but more than 70% reported that their visit at the Expert Center was their first contact with mental health services. Conclusions: To improve objective and subjective aspects of health outcome, gender differences and a wide range of co-occurring health conditions should be taken into account when designing healthcare provision for autistic adults. [ABSTRACT FROM AUTHOR]