Overexpression of miR-25 Downregulates the Expression of ROBO2 in Idiopathic Intellectual Disability.

Idiopathic intellectual disability (IID) encompasses the cases of intellectual disability (ID) without a known cause and represents approximately 50% of all cases. Neural progenitor cells (NPCs) from the olfactory neuroepithelium (NEO) contain the same information as the cells found in the brain, but they are more accessible. Some miRNAs have been identified and associated with ID of known etiology. However, in idiopathic ID, the effect of miRNAs is poorly understood. The aim of this study was to determine the miRNAs regulating the expression of mRNAs that may be involved in development of IID. Expression profiles were obtained using NPC-NEO cells from IID patients and healthy controls by microarray. A total of 796 miRNAs and 28,869 mRNAs were analyzed. Several miRNAs were overexpressed in the IID patients compared to controls. miR-25 had the greatest expression. In silico analysis showed that ROBO2 was the target for miR-25, with the highest specificity and being the most down-regulated. In vitro assay showed an increase of miR-25 expression induced a decrease in ROBO2 expression. In neurodevelopment, ROBO2 plays a crucial role in episodic learning and memory, so its down-regulation, caused by miR-25, could have a fundamental role in the intellectual disability that, until now, has been considered idiopathic.

Neuropsychological intervention in attention and visuospatial skills in two patients with Williams syndrome with different types of genetic deletion.

Williams Syndrome (WS) is a neurodevelopmental disorder with a distinctive physical, cognitive, and behavioral profile caused by a microdeletion in the q11.23 region of chromosome 7. The neuropsychological profile of WS is characterized by intellectual disability, hypersociability, and deficits, especially in attention and visuospatial skills. Our objective was to assess the effectiveness of a neuropsychological intervention program in attention and visuospatial skills in two patients with WS (aged 7 and 13 years old) with different types of deletion (1.5 and 1.8 Mb). Cognitive, behavioral, and adaptive abilities were evaluated through various neuropsychological tests and scales; the neuropsychological intervention program was subsequently applied, and we assessed its effectiveness. Both patients initially presented significant deficits in attention and visuospatial skills. After the program, we found improvements in attention and visuospatial skills. In addition, both patients had significant clinical advances and changes in adaptive behaviors (social and self-care). These findings suggest that this intervention program could improve attention processes, visuospatial skills, and some aspects of adaptive behavior in patients with WS, regardless of deletion size. Although the sample was small, limiting the generalizability of the results, we believe this program could be a helpful resource for professionals working with individuals with WS.

[The lag of genetic counseling in Mexico]. / El rezago del asesoramiento genético en México.

Genetic counseling is the process of advising indivduals, partners and families affected by or at risk of genetic disorders to help them understand and adapt to the medical, psychological, social, family and reproductive implications of a genetic condition. Given the expansion of precision medicine and the recent increase in the use of molecular diagnostic tests, it is necessary to have duly certified personnel in our environment to perform it. In Mexico, unlike other countries, the figure of the genetic counselor is not formally recognized, which is why geneticists doctors give this advice within the healthcare context (as part of the outpatient consultation). The number of these health professionals is below the internationally proposed requirement standard of one medical geneticist per 100,000 inhabitants, which is only met in Mexico City, making it of utmost importance to increase the training of medical geneticists as well such as the inclusion of these in the different health institutions of the country.

El asesoramiento genético es el proceso de comunicación que tiene como objetivo ayudar al individuo, la pareja o la familia a comprender y adaptarse a las implicaciones médicas, psicológicas, sociales, familiares y reproductivas de una condición genética. Dada la expansión de la medicina de precisión y el reciente incremento del uso de pruebas diagnósticas moleculares, es necesario contar en nuestro medio con personal debidamente certificado para realizarlo. En México, a diferencia de otros países, la figura del asesor en genética no está formalmente reconocida; por lo que médicos genetistas otorgan este asesoramiento dentro del contexto asistencial (formando parte de la consulta externa). El número de estos profesionales de la salud está por debajo del estándar de requerimiento propuesto internacionalmente, de un genetista por cada 100,000 habitantes, el cual únicamente se cumple en la Ciudad de México, por lo que resulta de suma importancia incrementar la formación de médicos genetistas, así como la inclusión de estos en las distintas instituciones de salud del país.

[Insights about uncertainty in genetic counseling]. / Una reflexión sobre la incertidumbre en el asesoramiento genético.

Genetic counseling is an information process to help people in the understanding and adaptation to the medical, psychological and family implications of the genetic contribution in diseases. This counseling encompasses all sorts of patients. This represents a challenge in the daily work of the medical geneticist, because giving information in a meaningful way to the patient and his family implies an emotional and psychological burden. Generally we can see two outcomes in the medical practice of genetics, which converge after a diagnosis process: 1) we can face the inability to reach a diagnostic conclusion or 2) we can establish or confirm a diagnosis with certainty, which is the main piece in the genetic counseling. However, in all the situations the uncertainty is a fact, since in the case of those individuals who come in for genetic counseling before symptoms appear or those in prenatal cases, the absence of clinical manifestations and the impossibility to change the course of events lead to the appearance of helplessness and despair. In those cases without diagnostic conclusion, this situation represents a reason for uncertainty, and even in those patients with a diagnosis, certain factors can modify the circumstances in which genetic counseling occurs, such as unpredictability or lack of control. Therefore, it is important to consider the management of uncertainty as an inherent part throughout the process of care in medical genetics. The teaching of medical genetics should also consider the inclusion of topics related to this circumstance.

El asesoramiento genético es un proceso de información para ayudar a las personas a adaptarse a las implicaciones médicas, psicológicas y familiares de la contribución genética en las enfermedades. Sus escenarios abarcan todo tipo de pacientes. Esto es un reto para el médico genetista, pues otorgar información de manera significativa al paciente y su familia conlleva una carga emotiva y psicológica. Hay dos desenlaces de la práctica médica en el área de la genética que convergen después de un proceso diagnóstico: 1) no llegar a una conclusión diagnóstica y 2) el resultado final confirma un diagnóstico de certeza alrededor del cual trata el asesoramiento genético. No obstante, en todas las situaciones la incertidumbre es un hecho patente, pues en aquellos individuos que acuden antes de la aparición de síntomas o en casos prenatales, la ausencia de manifestaciones clínicas y la imposibilidad de modificar el curso de los acontecimientos propician la aparición de impotencia y desolación. En los casos sin conclusión esto representa una razón de incertidumbre y en aquellos pacientes con un diagnóstico pueden presentarse factores que modifiquen las circunstancias en que se produce el asesoramiento genético, como la imprevisibilidad. Estos factores producen distintos grados de incertidumbre en aquellos que debieran beneficiarse con esta información; por tanto: el manejo de la incertidumbre es inherente al proceso de atención en genética médica. La enseñanza de la genética médica debe incluir tópicos relacionados a esta circunstancia durante el proceso.

[The role of the medical geneticist in the pediatric consultation]. / La participación del médico genetista en la consulta pediátrica.

The work of the medical geneticist is, from the clinical point of view, scarcely known. His healthcare-related activity requires close collaboration with specialists in different fields; hence, it is vital for the physician directly in charge of the patient to have at hand some useful recommendations in order to make care provided by the multidisciplinary team efficient and timely. The purpose of this paper is to outline some of the professional features of medical genetics specialists and to describe, in general terms, the work in clinical genetics, as well as to inform first contact clinicians - especially pediatricians - about the clinical and imaging studies they should order for patients with the most common congenital conditions before referring them for diagnostic or genetic counseling. It is important to point out that the communication process between the treating clinician and his/her patients (which in pediatric patients is with the family) is essential not only with regard to the reason for referral to the medical genetics department, but also for the family to be able to obtain information prior to the appointment, so that time and quality of care are improved once the genetics consultation takes place. Finally, this manuscript outlines the requirements for the communication between specialists, in order for them to promote and provide knowledge on medical genetics at all levels of care, for the benefit of patients.

El trabajo del médico genetista desde el punto de vista clínico es poco conocido. Su labor asistencial requiere la colaboración estrecha entre especialistas de diferentes ramas, por ello es vital que el médico directamente encargado del paciente tenga a la mano algunas recomendaciones para hacer eficiente y oportuna la atención del equipo multidisciplinario. La presente comunicación tiene como objetivo dar a conocer algunas características profesionales del médico genetista y describir a grandes rasgos su trabajo en el área clínica, además de informar a los médicos de primer contacto ­en especial a los pediatras­ de los estudios clínicos y de gabinete que deben solicitarse en los pacientes con los padecimientos congénitos más comunes, antes de enviarlos a diagnóstico o asesoramiento genético. Es importante destacar que el proceso de comunicación entre el médico tratante y la familia (en el caso de los pacientes pediátricos) es imprescindible no solo respecto al motivo del envío al servicio de genética médica, sino también para que la familia obtenga información previa a la cita y se mejore el tiempo y la calidad de la atención una vez en la consulta de genética. Por último, en este documento se plantean las necesidades de comunicación entre los especialistas, para que promuevan y aporten conocimientos en genética médica en todos los niveles de atención, en beneficio de los pacientes.