Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

Analytical Validation of a New Enzymatic and Automatable Method for d-Xylose Measurement in Human Urine Samples

Hypolactasia, or intestinal lactase deficiency, affects more than half of the world population. Currently, xylose quantification in urine after gaxilose oral administration for the noninvasive diagnosis of hypolactasia is performed with the hand-operated nonautomatable phloroglucinol reaction. This work demonstrates that a new enzymatic xylose quantification method, based on the activity of xylose dehydrogenase from Caulobacter crescentus, represents an excellent alternative to the manual phloroglucinol reaction. The new method is automatable and facilitates the use of the gaxilose test for hypolactasia diagnosis in the clinical practice. The analytical validation of the new technique was performed in three different autoanalyzers, using buffer or urine samples spiked with different xylose concentrations. For the comparison between the phloroglucinol and the enzymatic assays, 224 urine samples of patients to whom the gaxilose test had been prescribed were assayed by both methods. A mean bias of -16.08 mg of xylose was observed when comparing the results obtained by both techniques. After adjusting the cut-off of the enzymatic method to 19.18 mg of xylose, the Kappa coefficient was found to be 0.9531, indicating an excellent level of agreement between both analytical procedures. This new assay represents the first automatable enzymatic technique validated for xylose quantification in urine.The authors thank IgorMart´ın for his support with statistical analysis, Jos´e Claros and Ricardo Jara from Immunostep for their work in the kit development, and Guillermo Corrales for his technical assistance. The work presented in this manuscript was funded by Venter Pharma S.L., Madrid, Spain.Peer Reviewe

Pensar la Comunicación. Reflexiones y resultados de investigación. Tomo II

La investigación en comunicación pasa en la actualidad por momentos cruciales en la construcción de una teoría del conocimiento. No se conciben hoy los estudios en comunicación alejados de las ciencias humanas y sociales, pero tampoco, paradójicamente, alejados de las ciencias naturales y básicas. El estudio científico de la comunicación requiere de múltiples miradas complejas, desde las ciencias de la vida y de la conducta, hasta campos fundamentales como la etología, la filosofía, la cultura y la sociedad. Este libro intenta, de manera inconclusa por supuesto, ofrecer un aporte a este proceso desde la comunicación gráfica, el consumo, la ciudadanía, la televisión digital, los entornos virtuales de aprendizaje, la cultura digital y el cine, entre otros campos de conocimiento

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations

Biodiversity 2016. Status and Trends of Colombian Continental Biodiversity

This third volume of the annual report on biodiversity in Colombia continues the editorial line that begun in 2014. Using novel analytical and graphic proposals, these reports have the goal of communicating the contents to a broad public, making it available for discussion without sacrificing the quality of information. The challenge of communication continues to be a major part of the institutional project, and the new languages with which we are learning to communicate with society and other institutions are an experiment that we expect to be increasingly gratifying. The report for 2017 is already under construction and it counts on new digital technologies so the power of a colombian vital connection may be entirely expressed. The included content evidences that we are still far away from having a systematic follow-up about most of the topics related to the management of biodiversity and ecosystem services, which is the only way to evaluate the effectiveness of policies and investments made by society. In fact, a limitation that is recognized is that of identifying positive or negative changes that affect different levels of organization of life on this planet; therefore, our global navigation route of the Aichi targets is still to be verified. An additional purpose of this process includes the invitation of all Colombians to contribute in constructing and maintaining basic monitoring indicators for management since it is impossible to identify long-term trends of flora and fauna in the country without the support of institutions, researchers, and citizens. This challenge is immense in a megadiverse country such as Colombia. For this reason, the report will continue to open its pages to experts, and even indigenous peoples or local communities, for them to present their perspectives about environmental change and its effects on biodiversity in a systematic and documented manner. This has the objective of stimulating the commitment of everyone in the management of biodiversity and ecosystem services. The only way of overcoming the risk of extinction is through the active process of social learning in which all sectors assume a part of the complex responsibility in protecting the forms of life of the country, a roughly counted tenth of all creatures on Earth. I thank all the people that contributed in this Report, those who have supported us in the phases of production, and all readers and users, who are the ultimate judges of its utility.Bogotá, D. C

Biodiversidad 2016. Estado y Tendencias de la Biodiversidad Continental de Colombia

Esta tercera entrega del reporte anual de la biodiversidad en Colombia profundiza en la línea editorial iniciada el año 2014 mediante nuevas propuestas analíticas y gráficas, con la intención de garantizar que la información llegue a todos los públicos y pueda ser discutida de manera amena sin sacrificio de calidad. La apuesta comunicativa sigue siendo central en el proyecto institucional y los nuevos lenguajes con los que estamos aprendiendo a conversar con la sociedad y las instituciones son un experimento que esperamos sea cada vez más satisfactorio: ya estamos construyendo la versión 2017 con el apoyo de las nuevas tecnologías digitales de manera que la potencia de la conexión vital colombiana se exprese en toda su capacidad. Por los contenidos es evidente que aún distamos mucho de tener una capacidad de seguimiento sistemático para la mayoría de temas relativos a la gestión de la biodiversidad y los servicios ecosistémicos, la única manera de evaluar si las medidas de política y las inversiones que realiza la sociedad están teniendo los efectos deseados. De hecho, parte de las limitaciones reconocidas por robustamente los cambios positivos o negativos que afectan los diferentes niveles de organización de la vida planetaria, por lo cual las mismas metas de Aichi, nuestra carta de navegación global, están pendientes de verificación. Un propósito adicional de este proceso es la invitación a todos los colombianos para contribuir con la construcción y alimentación de los indicadores básicos de seguimiento a la gestión, ya que es imposible identificar las tendencias de largo plazo en que están inmersas la flora y fauna colombianas sin el apoyo de las instituciones, los investigadores y los ciudadanos: en el país de la megadiversidad, el reto es inmenso. Por este motivo, este reporte irá abriendo sus páginas a expertos, incluso indígenas o de comunidades locales, para que presenten de manera sistemática y documentada sus perspectivas del cambio ambiental y sus efectos en la biodiversidad, con el ánimo de promover el compromiso de todos en su gestión. La única manera de superar el riesgo de extinción es mediante un activo proceso de aprendizajes sociales que haga que todos los sectores asuman una parte de la compleja responsabilidad que significa proteger todas las formas de vida del país, una décima parte mal contada de las planetarias. Agradezco a las decenas de personas que contribuyeron con este reporte, a quienes nos han apoyado en todas las etapas de producción y a sus lectores y usuarios, quienes son en último término los jueces de su utilidad.Bogotá, D. C