Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels.

PURPOSE: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not. METHODS: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. RESULTS: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants. CONCLUSION: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.

La adolescencia en contexto: Representaciones Sociales en adolescentes de Medellín y Armenia, Colombia / Adolescence in a context: social representations in adolescents from Medellín and Armenia (Colombia)

Resumen Objetivo: Comprender las representaciones sociales de adolescencia en adultos y adolescentes de las ciudades de Medellín y Armenia. Método: Investigación cualitativa desde el enfoque procesual de la teoría de las representaciones sociales. La investigación se llevó a cabo en dos momentos: uno exploratorio y otro de profundización. Se realizó una evocación libre de palabras para identificar el núcleo central y los sistemas periféricos de la representación; a partir de esto, se realizaron grupos focales y entrevistas semiestructuradas que permitieron ampliar el horizonte de significado de la representación e identificar los procesos de objetivación y anclaje. En la investigación participaron 298 adolescentes habitantes de Medellín y Armenia. Resultados: El núcleo central para Armenia está constituido por la palabra "etapa", mientras que, en Medellín, se encuentra la "responsabilidad". Aunque en lo nuclear la representación en ambas ciudades comparte múltiples elementos, hay una diferencia fundamental respecto a la perspectiva de futuro, pues mientras para los adolescentes de Medellín es posible proyectar la vida en la adultez, para los adolescentes de Armenia prima el tiempo presente y no hay una delimitación del fin de la adolescencia. Conclusiones: La representación social de la adolescencia se ordena en torno a la idea de transición acompañada por diversos cambios; en este proceso, la reconfiguración de la relación con la familia y los amigos resulta fundamental. La experiencia de la adolescencia no es universal, pues el estrato socioeconómico, el nivel económico de la ciudad en que se vive y las posibilidades de desarrollo que ofrece, da un carácter diferencial al modo en que es significada y vivida.

Abstract Propose: Figure out social representations during adolescence in adults and teenagers from Medellín and Armenia (Colombia, South America). Method: A qualitative research study was conducted based on a theory of social representations. This research study was developed in two stages: an exploratory stage and the other, a deepening stage. In the exploratory stage, free evocation of words in order to identify a core and peripheral elements of social representations were produced. In the second stage, focus groups and semi-structured interviews to allow an expansion of meanings and to identify objectification and setting processes. The research involved 298 adolescents from Medellín and Armenia. Results: The core social representation for Armenia, is suggested by the word "stage", while, in Medellín, is "responsibility". Although, taking into account that there are many shared elements in relation with core social representations corresponding to each city, there is a fundamental difference related to a future perspective; this is because while for adolescents in Medellín is possible to project life into adulthood, for teenagers from Armenia present time prevails and there is no delimitation for the end of adolescence. Conclusions: Social representations related to adolescence is organized around the idea of transition with multiple changes. In this process, the relationship with family and friends become fundamental. The experience of adolescence is not considered universal; it is because the adolescent's socioeconomic status, economic level of a city where those adolescents live and also, the possibilities for development offered in a specific context, give a differential character to the way adolescence is represented and experienced.