Mutation update for the \u3cem\u3eSATB2\u3c/em\u3e gene

SATB2‐associated syndrome (SAS) is an autosomal dominant neurodevelopmental disorder caused by alterations in the SATB2 gene. Here we present a review of published pathogenic variants in the SATB2 gene to date and report 38 novel alterations found in 57 additional previously unreported individuals. Overall, we present a compilation of 120 unique variants identified in 155 unrelated families ranging from single nucleotide coding variants to genomic rearrangements distributed throughout the entire coding region of SATB2. Single nucleotide variants predicted to result in the occurrence of a premature stop codon were the most commonly seen (51/120 = 42.5%) followed by missense variants (31/120 = 25.8%). We review the rather limited functional characterization of pathogenic variants and discuss current understanding of the consequences of the different molecular alterations. We present an expansive phenotypic review along with novel genotype‐phenotype correlations. Lastly, we discuss current knowledge of animal models and present future prospects. This review should help provide better guidance for the care of individuals diagnosed with SAS

Speech, language, and feeding phenotypes of SATB2‐associated syndrome

SATB2‐associated syndrome (SAS) is a recently identified disorder characterized by neurodevelopmental deficits and craniofacial anomalies. Assessments of speech, language, and feeding‐related issues were conducted among 61 individuals with SAS (median age = 86 months, range = 26 months to 29 years of age). Individuals with SAS were mostly non‐verbal communicators (72.1%) with severe deficits in both language comprehension and expression. The majority of individuals had receptive vocabulary skills of a child younger than 3 years of age. Based on parent report, the average spoken lexicon was 28.6 (SD = 84.6, n = 55) with a range of 0 to 500 (median = 5 words). All of the individuals with SAS with enough verbal ability either showed signs of childhood apraxia of speech or already had a diagnosis (n = 40) and 73.3% exhibited problems with reliable communication with unfamiliar partners. Hypernasal resonance (17.8%) due to velopharyngeal insufficiency secondary to a history of cleft palate and/or apraxic palatal movement (60.0% of hypernasal patients with no history of cleft palate), problems with chewing (68.2%), overstuffing the mouth with solids (64.9%), pharyngeal phase dysphagia (60.8%), and sialorrhea (63.3%) were common in this population. Mutation type was not predictive of receptive or expressive language abilities. We developed language and communication treatment recommendations based on these findings

Smart Q-switching for single-pulse generation in an erbium-doped fiber laser

In this paper, we report an active Q-switching of an erbiumdoped fiber laser with special modulation functions and novel laser geometry. We experimentally demonstrate that using such a smart Q-switch approach, Q-switch ripple-free pulses with Gaussian-like shape and 17.3 ns width can be easily obtained. The idea behind the smart Q-switch is to suppress one of two laser waves contra-propagating along the fiber cavity, which arises after Q-cell opening, and to eliminate the minor sub-pulses

La imagen y la narrativa como herramienta para el abordaje psicosocial en escenarios de violencia. Departamentos de Casanare, Meta, Guaviare y Cundinamarca

Este trabajo contiene información sobre el abordaje psicosocial realizado a eventos violentos ocurridos en Colombia como causa del conflicto armado que por décadas ha dejados miles de personas víctimas de la violencia, para lo cual, se realizó el análisis a dos relatos de personas víctimas de la violencia; Carlos Arturo y peñas coloradas. Para ambos casos se realizó el análisis teniendo en cuenta los impactos psicosociales, los procesos de afrontamiento, transformación y superación del conflicto. Igualmente, se plantean una serie de estrategias y acciones que contribuyan a un impacto positivo en la población. Además, se encuentra plasmado un informe analítico de la imagen y la narrativa como instrumentos de identificación de factores psicosociales en escenarios de diversos tipos de violencia, en los departamentos de; Casanare, Meta, Guaviare y Cundinamarca. Se pretende dar a conocer o hacer visible la realidad de los territorios en cuanto al sufrimiento y destrucción que ha causado la violencia en Colombia, pero también, sensibilizar al lector a fin de generar empatía para con las personas que han sido víctimas del conflicto. Tratar de entender un poco a cerca de los factores influyentes en el desencadenamiento de la violencia y tratar de trabajar en cooperación para buscar estrategias que permitan ayudar a encontrar salida al conflicto y mejorar las condiciones de vida de la población. Si bien es cierto, la violencia, es una situación que causa diversas y complejas problemáticas sociales, es importante utilizar esas experiencias como conocimiento que permita avanzar en el desarrollo individual y social.This work contains information on the psychosocial approach carried out to violent events that occurred in Colombia as a cause of the armed conflict that for decades has left thousands of people victims of violence, for which, the analysis of two reports of people victims of violence was carried out.; Carlos Arturo and Peñas Coloradas. For both cases, the analysis was carried out taking into account the psychosocial impacts, the processes of coping, transformation and overcoming the conflict. Likewise, a series of strategies and actions are proposed that contribute to a positive impact on the population. In addition, an analytical report of the image and the narrative is embodied as instruments for the identification of psychosocial factors in scenarios of various types of violence, in the departments of; Casanare, Meta, Guaviare and Cundinamarca. It is intended to publicize or make visible the reality of the territories in terms of the suffering and destruction caused by violence in Colombia, but also to sensitize the reader in order to generate empathy for the people who have been victims of the conflict. Try to understand a little about the outstanding factors in the triggering of violence and try to work cooperatively to find strategies that help find a way out of the conflict and improve the living conditions of the population. Although it is true that violence is a situation that causes diverse and complex social problems, it is important to use these experiences as knowledge that allow progress in individual and social development

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia Bogotá.

Abordar las experiencias traumáticas de las personas, como consecuencia de haber estado inmersos en un conflicto, ya sea como víctimas o perpetradores, supone una alta responsabilidad para el profesional en psicología, actuando con un importante sentido ético y profesional que le permita indagar por las circunstancias que rodearon esa experiencia victimizante sin llegar a lesionar mediante una re traumatización o incluso provocando una alienación en la persona tratada. Precisamente esta fase del diplomado entrega a los psicólogos en formación una estrategia pensada a partir del análisis discursivo, que se apoya en los recursos de memoria para indagar sobre lo que represento para la víctima las experiencias vividas, apoyándose en los elementos del discurso, tratando de identificar y entender a qué le da valor la persona, para así devolver la identidad perdida, como nuevo recurso de afrontamiento. La importancia de la identidad se valora como recurso para que las personas cuenten con habilidades que les permitan saber cómo proceder en sus vidas, avanzar en los nuevos proyectos y ayuda a recobrar el valor otorgado a la vida, el cual con seguridad se encuentra lastimado (Estrada & Buitrago, 2016). En su contenido se podrá encontrar el análisis al relato de violencia y esperanza, en una mujer víctima del conflicto, nombrada como Jennifer, igualmente la consolidación de 9 preguntas que buscan decantar la información aportada por las víctimas, estructuradas de forma reflexiva, circulares y estratégicas. Como resultado de la revisión del caso Panduri, los integrantes del grupo colaborativo consolidan una serie de estrategias de tipo psicosocial, que buscan abordar integralmente a las víctimas, facilitándoles espacios orientativos para el desarrollo de sus vidas. El documento incluye un informe analítico, resultado de la realización de un ejercicio práctico de foto voz, integrando el componente intersubjetivo, conforme a las apreciaciones y percepciones abstraídas del entorno. En este proceso por contribuir a consolidar la identidad, así como los estados anímicos y emocionales de quien ha sido víctima del conflicto, se considera de relevancia el componente de saber preguntar, siendo una las habilidades que le aportan a transformar historias de victimización, en historias de esperanza. Para ello se busca crear espacios que inviten a la víctima a hablar, interactuar, facilitando la conversación y permitiendo que esta fluya de manera adecuada. La habilidad del psicólogo esta en lograr que sus preguntas extracten de la narrativa los recursos propios de la persona, sus sueños y propósitos, contribuyendo así como estrategia de reforzamiento a alcanzar una historia alternativa, donde la violencia que ha venido paralizando su vida, ya no sea la protagonista de su historia. Los relatos de violencia y luego de experiencias transformadoras, abordados por cada integrante del grupo colaborativo se toman como elementos constitutivos de aprendizaje que potencian la reconstrucción de nuevas formas de avanzar en la historia, garantizando la construcción de una nueva identidad, integrada por atributos, valores, creencias, rasgos de personalidad, que fortalezcan el capital social tan afectado por la ausencia de recursos psicosociales.Address traumatic experiences of people, as a result of having been immersed in a conflict, either as victims or victimizers, a high responsibility for the professional in psychology, act with significant ethical and professional meaning that allows you to inquire about the circumstances that they surrounded that victimizing experience without reaching an injury due to traumatization or even provoking an alienation in the person treated. Precisely this phase of the diploma gives psychologists in the formation of a strategy designed from the discursive analysis, which is based on memory resources to investigate what the victim represents for the experiences lived, supporting the elements of the speech, trying to identify and understand what the value of the person is, in order to return the lost identity, as a new coping resource. The importance of identity is adapted as a resource for people to have skills that allow them to know how to proceed in their lives, advance in new projects and help recover the value given to life, which is sure to be find hurt (Estrada & Buitrago, 2016). In this process, in order to contribute to consolidate the identity, as well as the emotional and emotional states of the victim of the conflict, the component of knowing how to ask is considered relevant, being the skills that contribute to the transformations of victimization histories, in the stories of hope. To do this, we seek to create spaces that invite the victim to speak, interact, facilitate the conversation and allow it to flow properly. The psychologist's ability is to get the questions to extract the narrative from the person's own resources, their dreams and purposes, thus contributing to the strategy of reinforcing an alternative story, where the violence that has paralyzed his life, no longer Sea the protagonist of its history. The stories of violence and then of transformative experiences, addressed by each member of the collaborative group are taken as constitutive elements of learning that enhance the reconstruction of new ways of advancing in history, guaranteeing the construction of a new identity, integrated by attributes, values , beliefs, personality traits, that strengthen the social capital so affected by the absence of psychosocial resources

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia –Bogotá D.C, Departamento Cundinamarca y Departamento del Cesar.

El conflicto social colombiano desarrollado después de la década de los años cuarenta, generó un sinnúmero de víctimas con prácticas de eliminación física incluidas la tortura, el asesinato selectivo, el desplazamiento forzado y en épocas recientes el narcotráfico profundizó la degradación de las prácticas de guerra desde los actores armados legales e ilegales. Las víctimas del conflicto armado suelen ser, en muchos casos revictimizadas, a expensas de lograr la reparación por vía administrativa quedan imbuidos en una excesiva tramitología qué en muchos casos terminan colmando la paciencia de quiénes han sufrido los efectos del conflicto. El caso de Modesto Pacaya muestra la política de reclutamiento impuesta por los actores armados ilegales en los territorios bajo su dominio, produciendo el rompimiento de los vínculos con las diferentes redes de apoyo, acompañado de la vulneración de los derechos del sujeto. La narrativa se convierte en una instrumento poderoso para el acompañamiento psicosocial, ya que a través de esta se pueden tramitar los duelos y se pueden encontrar nuevas versiones alternas a la historia victimizante siendo una herramienta útil para encontrar estrategias y nuevos posibles, que logre la transformación de las historias de los individuos en experiencias vitales dotadas de nuevos significados, entre ellos la esperanza y la resignificación como claves para salir de la situación de víctima. Las víctimas del desplazamiento de Peñas Coloradas evidencian los emergentes psicosociales que producen daños psicosociales a los habitantes, sin embargo, a través de las narrativas las víctimas logran describir nuevos escenarios que propician un nuevo tejido social, la restauración del pan de vida y la consideración de ser sujetos de derechos. La foto voz como ejercicio de la memoria es una construcción simbólica que permite a las víctimas ver el pasado de manera prospectiva considerado las posibles versiones que existen acerca de su situación, destacando los recursos necesarios para abandonar la categoría de víctima y destacar estrategias que logran detectar discursos dominantes y propician nuevos escenarios de organización social para las víctimas con lo cual pueden reconstruir su tejido social y de vida.The Colombian social conflict developed after the decade of the forties, generated countless victims with practices of physical elimination including torture, selective assassination, forced displacement and in recent times drug trafficking deepened the degradation of war practices since legal and illegal armed actors. The victims of the armed conflict tend to be, in many cases re-victimized, at the expense of achieving administrative reparation, they are imbued with excessive red tape which in many cases ends up wearing down the patience of those who have suffered the effects of the conflict. The case of Modesto Pacayá shows the recruitment policy imposed by illegal armed actors in the territories under their control, producing the breaking of ties with the family support network accompanied by the violation of the rights of the subject. The narrative becomes a powerful tool for psychosocial accompaniment, since through it mourning can be processed and new alternate versions of the victimized story can be found, being a useful tool to find strategies and new possibilities that achieve the transformation of the stories of individuals into life experiences endowed with new meanings, including hope and resignification as keys to get out of the situation of victim. The victims of the displacement of Peñas Coloradas evidence the psychosocial emergents that produce psychosocial damage to the inhabitants, however, through the narratives the victims manage to describe new scenarios that foster a new social fabric, the reconstruction of the life project and the consideration of being subjects of rights. The voice photo as an exercise of memory is a symbolic construction that allows victims to see the past prospectively, considering the possible versions that exist about their situation, highlighting the resources necessary to abandon the category of victim and highlighting strategies that manage to detect dominant discourses and propitiate new scenarios of social organization for the victims with which they can rebuild their social and life fabric

Genotype and Phenotype in 12 additional individuals with SATB2-Associated Syndrome

SATB2-associated syndrome (SAS) is a multisystemic disorder caused by alterations of the SATB2 gene. We describe the phenotype and genotype of 12 individuals with 10 unique (de novo in 11 of 11 tested) pathogenic variants (1 splice site, 5 frameshift, 3 nonsense, and 2 missense) in SATB2 and review all cases reported in the published literature caused by point alterations thus far. In the cohort here described, developmental delay (DD) with severe speech compromise, facial dysmorphism, and dental anomalies were present in all cases. We also present the third case of tibial bowing in an individual who, just as in the previous 2 individuals in the literature, also had a truncating pathogenic variant of SATB2. We explore early genotype-phenotype correlations and reaffirm the main clinical features of this recognizable syndrome: universal DD with severe speech impediment, mild facial dysmorphism, and high frequency of craniofacial anomalies, behavioral issues, and brain neuroradiographic changes. As the recently proposed surveillance guidelines for individuals with SAS are adopted by providers, further delineation of the frequency and impact of other phenotypic traits will become available. Similarly, as new cases of SAS are identified, further exploration of genotype-phenotype correlations will be possible

Case Report: SATB2-Associated Syndrome Overlapping With Clinical Mitochondrial Disease Presentation: Report of Two Cases

SATB2-associated syndrome (SAS) is an autosomal dominant neurogenetic multisystemic disorder. We describe two individuals with global developmental delay and hypotonia who underwent an extensive evaluation to rule out an underlying mitochondrial disorder before their eventual diagnosis of SAS. Although the strict application of the clinical mitochondrial disease score only led to the designation of “possible” mitochondrial disorder for these two individuals, other documented abnormalities included nonspecific neuroimaging findings on magnetic resonance imaging and magnetic resonance spectroscopy, decreased complex I activity on muscle biopsy for patient 2, and variation in the size and relative proportion of types of muscle fibers in the muscle biopsies that were aligned with mitochondrial diseases. SAS should be in the differential diagnoses of mitochondrial disorders, and broad-spectrum diagnostic tests such as exome sequencing need to be considered early in the evaluation process of undiagnosed neurodevelopmental disorders

CDK19-related disorder results from both loss-of-function and gain-of-function de novo missense variants

Purpose To expand the recent description of a new neurodevelopmental syndrome related to alterations in CDK19. Methods Individuals were identified through international collaboration. Functional studies included autophosphorylation assays for CDK19 Gly28Arg and Tyr32His variants and in vivo zebrafish assays of the CDK19(G28R) and CDK19(Y32H). Results We describe 11 unrelated individuals (age range: 9 months to 14 years) with de novo missense variants mapped to the kinase domain of CDK19, including two recurrent changes at residues Tyr32 and Gly28. In vitro autophosphorylation and substrate phosphorylation assays revealed that kinase activity of protein was lower for p.Gly28Arg and higher for p.Tyr32His substitutions compared with that of the wild-type protein. Injection of CDK19 messenger RNA (mRNA) with either the Tyr32His or the Gly28Arg variants using in vivo zebrafish model significantly increased fraction of embryos with morphological abnormalities. Overall, the phenotype of the now 14 individuals with CDK19-related disorder includes universal developmental delay and facial dysmorphism, hypotonia (79%), seizures (64%), ophthalmologic anomalies (64%), and autism/autistic traits (56%). Conclusion CDK19 de novo missense variants are responsible for a novel neurodevelopmental disorder. Both kinase assay and zebrafish experiments showed that the pathogenetic mechanism may be more diverse than previously thought.Peer reviewe

Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2

SATB2-Associated syndrome (SAS) is an autosomal dominant, multisystemic, neurodevelopmental disorder due to alterations in SATB2 at 2q33.1. A limited number of individuals with 2q33.1 contiguous deletions encompassing SATB2 (ΔSAS) have been described in the literature. We describe 17 additional individuals with ΔSAS, review the phenotype of 33 previously published individuals with 2q33.1 deletions (n = 50, mean age = 8.5 ± 7.8 years), and provide a comprehensive comparison to individuals with other molecular mechanisms that result in SAS (non-ΔSAS). Individuals in the ΔSAS group were often underweight for age (20/41 = 49%) with a progressive decline in weight (95% CI = −2.3 to −1.1, p \u3c 0.0001) and height (95% CI = −2.3 to −1.0, p \u3c 0.0001) Z-score means from birth to last available measurement. ΔSAS individuals were often noted to have a broad spectrum of facial dysmorphism. A composite image of ΔSAS individuals generated by automated image analysis was distinct as compared to matched controls and non-ΔSAS individuals. We also present additional genotype–phenotype correlations for individuals in the ΔSAS group such as an increased risk for aortic root/ascending aorta dilation and primary pulmonary hypertension for those individuals with contiguous gene deletions that include COL3A1/COL5A2 and BMPR2, respectively. Based on these findings, we provide additional care recommendations for individuals with ΔSAS variants