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

Opinión De Un Grupo De Expertos Sobre Facilitadores Para La Implantación Del Seguimiento Farmacoterapéutico En Las Farmacias Comunitarias Españolas - Opinion of a group of experts on facilitators for introducing pharmacotherapy follow up in Spanish communities

A focus group, consisting of members of the Community Pharmacy Pharmaceutical Care Forum, was created as part of a research study into prioritising facilitators for introducing pharmaceutical follow-up in Spanish community pharmacies The aim was to explore their options regarding the facilitators prioritised in this study that had been defined as “Incentives”, “External Campaigns”, “Expertise in Pharmacotherapy Follow-Up Service” and “Pharmacist Professionalism”. The priority facilitator of the study, “Incentives”, mainly includes economic incentives, which are essential for the introduction and sustainability of pharmacotherapy follow-up services, although they also refer to other kinds of incentive, such as professional recognition. The participants agreed with the results of the study, which indicate the need for a preliminary payment to introduce new professional services. It is considered that this payment is justified by the benefits that the pharmacotherapy follow-up service offers patients’ health and the reduction in health expenses derived from the correct use of medication. Therefore, various methods of economic incentives for pharmacists who offer pharmacotherapy follow-up services were proposed. As far as professional recognition is concerned, the accreditation of the pharmacy that offers pharmacotherapy follow-up services was considered to be an incentive, and that this service should be relevant at a curricular level. Carrying out external campaigns as well as the existence of a professional pharmaceutical expert, qualified and accredited to offer the new professional pharmaceutical services (PPS) were also confirmed as being very important

Opinión de un grupo de expertos sobre facilitadores para la implantación del seguimiento farmacoterapéutico en las farmacias comunitarias españolas

En el contexto de un estudio de investigación sobre priorización de facilitadores para la implantación del Seguimiento Farmacoterapéutico en las farmacias comunitarias españolas, se realizó un grupo focal compuesto por miembros de Foro de Atención Farmacéutica en Farmacia Comunitaria. El objetivo era explorar sus opiniones sobre los facilitadores priorizados en dicho estudio que se habían definido como “Incentivos”, “Campañas externas”, “Experto en SFT” y “Profesionalidad del farmacéutico”. El facilitador prioritario del estudio, denominado “incentivos”, incluye fundamentalmente incentivos económicos, imprescindibles en la implantación y sostenibilidad del Seguimiento Farmacoterapéutico, aunque también hace referencia a otro tipo de incentivo como el reconocimiento profesional. Los participantes estaban de acuerdo con los resultados del estudio, que indican la necesidad de un pago previo para implantar nuevos servicios profesionales. Se considera que este pago queda justificado por los beneficios que la realización del Seguimiento Farmacoterapéutico aporta a la salud del paciente y a la reducción del gasto sanitario derivado de un buen uso de la medicación. Por consiguiente, se plantearon distintos métodos para incentivar económicamente a la farmacia que realiza Seguimiento Farmacoterapéutico. En cuanto al reconocimiento profesional, se consideró como un incentivo la acreditación de la farmacia que realiza SFT y que su provisión tenga relevancia a nivel curricular. Se confirma también como de gran importancia tanto la realización de campañas externas como la existencia de un experto farmacéutico profesional, preparado y acreditado para realizar nuevos SPF

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