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

The development of a testosterone stimulation test in the virginia opossum (Dedelphis virginiana) and its use in evaluating deslorelin contraception

The aims of the present study were to examine the variability of testosterone secretion in the Virginia Opossum over a 24 h period and to develop a testosterone stimulation test that would provide an index of the prevailing testosterone biosynthetic capacity of the testes; the latter was used to clinically evaluate the efficacy of a gonadotrophin-releasing hormone agonist contraceptive. Sexually-mature captive opossums (n = 12) located in Africam Safari (Mexico) sampled every 12 h over 24 h consistently showed basal

Encuentros. Revista de Ciencias Humanas, Teoría Social y Pensamiento Critico. Segunda Época (Año 6 no. 7 ene-jul 2018)

ENCUENTROS. REVISTA DE CIENCIAS HUMANAS, TEORÍA SOCIAL Y PENSAMIENTO CRÍTICO es una revista auspiciada por el Centro de Estudios Geo-Históricos y Socio-Culturales de la Universidad Nacional Experimental Rafael María Baralt. Su publicación es periódica (semestral). Es una revista que se define como un medio alternativo que asume el compromiso de analizar y reflexionar sobre los procesos, dinámicas y coyunturas históricas que viven y sienten nuestras sociedades. También es un proyecto que acompaña los aportes a nuevas teorías para re-interpretar nuestro devenir histórico. De manera que es una revista crítica y decolonial. Sus áreas temáticas abordan las CIENCIAS HUMANAS (Filosofía, Historia, Educación, Letras) TEORIAS SOCIALES (Antropología, Sociología,) Y EL PENSAMIENTO CRITICO ALTERNATIVO (Interculturalidad, Epistemologías del sur, Filosofía de la Liberación, Decolonialidad) fundado en Latinoamérica.Presentacion p.9 / El rol emancipador de la episteme politica intercultural en America Latina p.11 / Una mira critica al proceso politico del movimiento indigena boliviano y su apuesta en la refundacion del Estado p.11 / Pensar al Estado: democracia y plurinacionalidad. Aportes teóricos de Álvaro García Linera p.63 / Jean Paul Sartre: breves reflexiones sobre su pensamiento anticolonial p.77 / La Genealogía como método histórico-filosófico para el estudio de la cultura organizacional pública. p.91 / El pensamiento venezolano expresado en las obras de Teresa de la Parra, María Calcaño y Lydda Franco p.115 / Entrevista a Edward Govia: Transformación Universitaria p.131 / Formación Histórica del Movimiento Indígena Boliviano.Autor: Huáscar Salazar Lohman p.145 / Instrucciones para los autores p.14

Encuentros. Revista de Ciencias Humanas, Teoría Social y Pensamiento Critico. Segunda Época (Año 6 no. 7 ene-jul 2018)

ENCUENTROS. REVISTA DE CIENCIAS HUMANAS, TEORÍA SOCIAL Y PENSAMIENTO CRÍTICO es una revista auspiciada por el Centro de Estudios Geo-Históricos y Socio-Culturales de la Universidad Nacional Experimental Rafael María Baralt. Su publicación es periódica (semestral). Es una revista que se define como un medio alternativo que asume el compromiso de analizar y reflexionar sobre los procesos, dinámicas y coyunturas históricas que viven y sienten nuestras sociedades. También es un proyecto que acompaña los aportes a nuevas teorías para re-interpretar nuestro devenir histórico. De manera que es una revista crítica y decolonial. Sus áreas temáticas abordan las CIENCIAS HUMANAS (Filosofía, Historia, Educación, Letras) TEORIAS SOCIALES (Antropología, Sociología,) Y EL PENSAMIENTO CRITICO ALTERNATIVO (Interculturalidad, Epistemologías del sur, Filosofía de la Liberación, Decolonialidad) fundado en Latinoamérica.Presentacion p.9 / El rol emancipador de la episteme politica intercultural en America Latina p.11 / Una mira critica al proceso politico del movimiento indigena boliviano y su apuesta en la refundacion del Estado p.11 / Pensar al Estado: democracia y plurinacionalidad. Aportes teóricos de Álvaro García Linera p.63 / Jean Paul Sartre: breves reflexiones sobre su pensamiento anticolonial p.77 / La Genealogía como método histórico-filosófico para el estudio de la cultura organizacional pública. p.91 / El pensamiento venezolano expresado en las obras de Teresa de la Parra, María Calcaño y Lydda Franco p.115 / Entrevista a Edward Govia: Transformación Universitaria p.131 / Formación Histórica del Movimiento Indígena Boliviano.Autor: Huáscar Salazar Lohman p.145 / Instrucciones para los autores p.14

Differences in <i>Cx</i>. <i>quinquefasciatus</i> larvae exposed to different insecticides relative to unexposed.

<p>Differences in <i>Cx</i>. <i>quinquefasciatus</i> larvae exposed to different insecticides relative to unexposed.</p

Mean and observed measurements of identified metabolites.

<p>Arg, C0, and C2 from left to right. Each dot corresponds to a sample. Crossed circle represent the mean for each treatment group. The vertical axis shows the measurements. The horizontal axis represents samples and treatment groups.</p

Heat map representing concentration of metabolites analyzed.

<p>Columns to the left show the p-value showing statistical significance in red. Insecticides (chlorpyrifos, permethrin and temephos) and the control group (larvae unexposed) are shown in first columns. Acronyms on the right are the metabolites. In the heat map, blue, white, and red, indicates low, median and high concentration, respectively.</p

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 &gt; T (p.Arg1129Leu) in ABCA4 and c.2276G &gt; 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