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

Datos sobre actividad de anfibios y pequeños reptiles de Doñana (Huelva, España)

El estudio se ha realizado en base a la observación y captura de individuos mediante dos métodos: 1) censos nocturnos usado sólo para los anfibios, 2) control de una serie de losetas, dispuestas previamente, bajo las que se cobijan anfibios y reptiles. Para los anfibios, la mayor actividad se concentra en los meses más lluviosos, mientras que parece existir un período de inactividad durante el verano. Los dos métodos empleados detectan sólo la actividad terrestre, por lo que las especies de actividad muy ligada al medio acuático aparecen escasamente representadas. Entre los reptiles, la mayoría de las observaciones corresponden a Podarcis hispanica, que llega a instalarse bajo las losas, así como Blanus cinereus que aparece en menor número. Otras especies, por el contrario, las utilizan solamente como un refugio transitorio. Se describen algunas características del habitat utilizado por las especies observadas.The study was carried out throughout two different methods: 1) Night census of individuals, from a car at a constant slow speed, used only for amphibians, 2) Control of individuals refuged under flag-stones placed in the study area. Main activity of amphibians occurs in most rainy months, while a no activity period seems to occur in summer months. The methods employed detected terrestrial activity of animals, thus a poor information was obtained on species of aquatic activity. Most information recorded on reptiles is about Podarcis hispanica, a species which can use the tiles as a long time refuge. Blanus cinereus is considered as an usual dweller under the tiles, despite the number of individual captured is not large enough. Other species only inhabit them as a temporary refuge, appearing sporadically. Some habitat characteristics of species recorded are described

Estudio sistemático y morfológico de la Palinología miocena de la región suroriental de la Depresión del Duero (España). II: Gymnospermae

[ES] Se describe la morfología polínica de las Gimnospermas identificadas en el sector sur-oriental de la Depresión del Duero, en depósitos que corresponden al Aragoniense superior - Vallesiense (ARMENTEROS, 1986). Taxonómicamente se han reconocido las familias Pinaceae, Cupressaceae, Taxodiaceae, Cycadaceae y Zamiaceae.[EN] Pollen morphology of the Gymnospermae from the South-eastern Duero Basin (Spain) is described. The deposits analyzed belong to Upper Aragonian - Vallesian age (ARMENTEROS, 1986). Pinaceae, Cupressaceae, Taxodiaceae, Cyacadaceae and Zamiaceae have been recognized in this region

Estudio sistemático y morfológico de la Palinología miocena de la región suroriental de la Depresión del Duero (España). I: Esporas

[ES] Se estudian de modo sistemático las esporas, correspondientes a las divisiones Bryophyta y Pteridophyta, encontradas en la región suroriental de la Depresión del Duero y que según ARMENTEROS (1986) se encuadra en el lapso Aragoniense superior-Vallesiense. En el trabajo se indican además su morfología, litología en la que se encuentran y distribución geográfica.[EN] Spores of Bryophyta and Pteridophyta coming from the south-eastern region of the Duero Basin (Spain) have been studied from systematic and morphological points of view. According to ARMENTEROS (1986) the sediments analyzed are included in the Upper Aragonian-Vallesian passage of the continental miocène deposits. A locality map is given as well as a table snowing the number of specimens and samples which yielded the spores described.

Miocene microflora of Belorado (Spain)

Neogene deposits from Belorado (Province de Burgos, Spain) in the NE border of the Duero Basin have been analyzed. The palynologic analysis of the samples suggests the existence of arboreal landscapes associated with the herbaceous cover creating belts of vegetation around restricted aquatic areas (marshy and lacustrine environments). The characteristics of the palynomorph assemblages allow to define a warm-template climate with strong seasons. The age of these deposits could be included in the middle Miocene (Aragonian)

Moluscos, Ostrácodos y Palinología de las facies fluvio-lacustres del Neógeno del SE de la provincia de Valladolid (Cuenca del Duero)

The Mollusca, Ostracoda, Foraminifera and Palino/gy from 14 localities in the Eastern Neogene of Valladolid (Duero Basin) are studied. Differents stratigraphic levels are included in the Facies «Dueñas», «Zaratán», «Cuestas» and «Caliza de los Páramos» units. The Mollusca are found in the lacustrine facies and are essentially dominated by Gyraulus. The qualitative and quantitative analysis of Ostracoda-Foraminifera associations are indicative of paleosalinities; increase in salinity is pointed by Candonidae-llyocypris, llyocypris-Cyprinotus, Cyprinotus-Cyprideis- Foraminifera, successively. In general, the samples are poore in palinomorphs and richev in microalgal component