Avances genómicos de la última década y su influencia en el enfoque diagnóstico de la discapacidad intelectual.

Human intelligence is a polygenic trait (~1000 genes), with an approximate influence of 0.1% per every individual gen. It is an indispensable attribute for personal, familial, social, and economic development; furthermore, it is directly proportional to health maintenance and a longer life expectancy. Consequently, intellectual disability affects all these areas, and constitutes a public health problem in several Latin American countries where it shows a >10%. In ~85% of the patients, the etiology of intellectual disability, be that isolated or syndromic; it is mostly diagnosed through the new technological search studies of the genome, such as new generation sequencing and/or chromosomal microarray analysis. The clinical and etiological diagnosis of intellectual disability, when duly confirmed, allows the choice of specific treatment modalities, the precise determination of prognosis, and the estimation of individual or familial recurrence risks.La inteligencia humana es un rasgo poligénico (~1000 genes) con una influencia de cada gen aproximadamente ascendente al 0,1%. Es un atributo indispensable para el desarrollo personal, familiar, social y económico y tiene, además, una relación directamente proporcional al mantenimiento de la salud y a una mayor esperanza de vida. La discapacidad intelectual, consecuentemente, afecta todas estas áreas y constituye un problema de salud pública en varios países de Latinoamérica en los que exhibe una prevalencia mayor al 10%. La etiología de la discapacidad intelectual sea aislada o sindrómica, es genética hasta en un 85% de los casos; se diagnostica mediante las nuevas tecnologías de búsqueda en el genoma, tales como la secuenciación masiva y el análisis cromosómico por micromatrices. El diagnóstico etiológico de la discapacidad intelectual permite la selección de terapias específicas, la determinación del pronóstico y de riesgos de recurrencia familiar e individual

Análisis retrospectivo de las características clínicas y moleculares de 40 pacientes con distrofia muscular de Duchenne y de Becker en el Hospital Nacional Guillermo Almenara Irigoyen, 1997 - 2007

Publicación a texto completo no autorizada por el autorEl documento digital no refiere asesorDetermina las características clínicas y moleculares de pacientes con sospecha clínica de la distrofia muscular de Duchenne y de Becker en el Hospital Nacional Guillermo Almenara Irigoyen entre los años 1997 y 2007. Se recolecta la información clínica, análisis de laboratorio y estudios moleculares de 93 pacientes atendidos en dicho hospital.Tesi

Tratamiento de las enfermedades genéticas: Presente y futuro: Management of genetic diseases: Present and future

Today, the number of genetic diseases is around 10000 conditions, affecting to 6%-8% of all populations. This review shows us how the discovery of genetic variants in our genome, this facilitated to know with precision about the mechanisms physiopathological, and hence to recognize those target points susceptible to modifications, through therapeutical strategies different with palliative proposals, increase life expectancy, or improve qualities of life. These therapies are diverse, using drugs for polygenic diseases, nutritional therapy, special formulas, enzyme replacement therapies, hematopoietic stem cell transplant, substrate reduction, oligonucleotides, and gene therapy. These genetic diseases are heterogeneous clinically with a very low frequency; nevertheless, open to the possibility of research in new strategies for more genetic disease, that today, furthermore, are orphans.  El número de enfermedades genéticas se estima que podrían ser más de 10 000 condiciones diferentes, afectando alrededor del 6-8% de la población. La presente revisión nos muestra la importancia del descubrimiento de las variantes patogénicas en nuestro genoma que nos permite conocer con mayor precisión cuales son los mecanismos fisiopatológicos, y por lo tanto conocer puntos dianas susceptibles de modificaciones, mediante diferentes estrategias terapéuticas para poder palear los síntomas y signos, aumentar la expectativa de vida, mejorando así la calidad de vida de los pacientes que tienen algunas de estas enfermedades genéticas. Las diferentes terapias que existen en la actualidad son muy diversas como fármacos de uso en patologías comunes, terapia nutricional, fórmulas especiales, terapias de reemplazo enzimático, trasplante de órganos y células hematopoyéticas, reducción de sustrato, oligonucleótidos y la terapia génica. Al ser las enfermedades genéticas clínicamente heterogéneas, abre la posibilidad de poder investigar cada vez más nuevas estrategias en un mayor número de enfermedades que en la actualidad están olvidadas. &nbsp

Considerações éticas e científicas do início da vida sobre o aborto eugênico em enfermidades genéticas incapacitantes no Peru

The article presents current biological concepts, as well as some philosophical approaches to the beginning of life, which will be examined in relation to the need for eugenic abortion. The concept of “exdurantism” is presented, in which the combination of the new nuclear and mitochondrial genome makes the individual unique; furthermore, the genomic complex is conceived as a "somatic integrator" that directs embryonic development, and the problematic is shown in the case of rape that causes pregnancies, eugenic abortion in incapacitating genetic diseases or the use of embryos after in-vitro fertilization. The dignity of the person begins at conception. When a serious or lethal genetic disease is detected, economic and social support, diagnosis and treatment should be offered; in addition, public health should invest more in screening, diagnosis, management and research strategies.El artículo expone conceptos actuales biológicos, así como algunos planteamientos filosóficos acerca del inicio de la vida, que se examinarán en relación con la necesidad del aborto eugenésico. Se presenta el concepto de “exdurantismo”, en el que la combinación del nuevo genoma nuclear y mitocondrial hacen único al individuo; además, se concibe al complejo genómico como “integrador somático” que dirige el desarrollo embrionario, y se muestra la problemática en el caso de las violaciones que provocan embarazos, el aborto eugenésico en enfermedades genéticas incapacitantes o la utilización de embriones posterior a la fertilización in-vitro. Se plantea que la dignidad de la persona comienza desde la concepción. Frente a la detección de una enfermedad genética, grave o letal, se debe ofrecer soporte económico y social, de diagnóstico y tratamiento; además, desde la salud pública, una mayor inversión para plantear estrategias de tamizaje, diagnóstico, manejo e investigación.O artigo apresenta conceitos biológicos atuais, bem como algumas abordagens filosóficas sobre o início da vida, que serão examinados em relação à necessidade do aborto eugênico. É apresentado o conceito de “exdurantismo”, no qual a combinação do novo genoma nuclear e mitocondrial torna o indivíduo único; além disso, o complexo genômico é concebido como um "integrador somático" que dirige o desenvolvimento embrionário, e é mostrada a problemática no caso de estupro que resulta em gravidez, aborto eugênico em doenças geneticamente incapacitantes ou o uso de embriões após a fertilização in vitro. Argumenta-se que a dignidade da pessoa começa na concepção. Diante da detecção de uma doença genética, grave ou letal, devem ser oferecidos apoio econômico e social, diagnóstico e tratamento, bem como maior investimento em saúde pública em estratégias de triagem, diagnóstico, gestão e pesquisa

Importance about use of high-throughput sequencing in pediatric: case report of a patient with Fanconi-Bickel syndrome

Abstract Background Fanconi-Bickel syndrome is characterized by hepatorenal disease caused by anomalous glycogen storage. It occurs due to variants in the SLC2A2 gene. We present a male patient of 2 years 7 months old, with failure to thrive, hepatomegaly, metabolic acidosis, hypophosphatemia, hypokalemia, hyperlactatemia. Results Exome sequencing identified the homozygous pathogenic variant NM_000340.2(SLC2A2):c.1093 C > T (p.Arg365Ter), related with Fanconi-Bickel syndrome. He received treatment with bicarbonate, amlodipine, sodium citrate and citric acid solution, enalapril, alendronate and zolendronate, and nutritional management with uncooked cornstarch, resulting in an improvement of one standard deviation in weight and height. Conclusions The importance of knowing the etiology in rare genetic disease is essential, not only to determine individual and familial recurrence risk, but also to establish the treatment and prognosis; in this sense, access to a new genomic technology in low- and middle-income countries is essential to shorten the diagnostic odyssey

Williams-Beuren syndrome in diverse populations

Williams–Beuren syndrome (WBS) is a common microdeletion syndrome characterized by a 1.5Mb deletion in 7q11.23. The phenotype of WBS has been well described in populations of European descent with not as much attention given to other ethnicities. In this study, individuals with WBS from diverse populations were assessed clinically and by facial analysis technology. Clinical data and images from 137 individuals with WBS were found in 19 countries with an average age of 11 years and female gender of 45%. The most common clinical phenotype elements were periorbital fullness and intellectual disability which were present in greater than 90% of our cohort. Additionally, 75% or greater of all individuals with WBS had malar flattening, long philtrum, wide mouth, and small jaw. Using facial analysis technology, we compared 286 Asian, African, Caucasian, and Latin American individuals with WBS with 286 gender and age matched controls and found that the accuracy to discriminate between WBS and controls was 0.90 when the entire cohort was evaluated concurrently. The test accuracy of the facial recognition technology increased significantly when the cohort was analyzed by specific ethnic population (P-value < 0.001 for all comparisons), with accuracies for Caucasian, African, Asian, and Latin American groups of 0.92, 0.96, 0.92, and 0.93, respectively. In summary, we present consistent clinical findings from global populations with WBS and demonstrate how facial analysis technology can support clinicians in making accurate WBS diagnoses