Results of implementation of new genomics in spanish national health system

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In Spain, Inherited Retinal Dystrophies (IRD) gene diagnosis has been implemented from several decades ago (from 90's of last century), throughout the collaborative and multidisciplinary work of six teams located around the country (EsRetNet https://www.esretnet.org/, and others).Along this time, we have developed guidelines to extend and improve gene testing for IRD in Spain (Ministry of Health, 2019 (https://portal.guiasalud.es/gpc/distrofias-hereditarias-retina/), and different molecular approaches have been implemented to increase the rate of molecular characterization of the patients, rising next generation sequencing (NGS) for routine, in 2013.In January 2024, the pipeline for Gene testing in Spanish National Health System (NHS) was released, including ophthalmological genetic disorders (https://cgen.sanidad.gob.es/#/). This pipeline defines the conditions to be studied, using ICD 10 and ORPHA codification, the reasons to refer, and the molecular procedures to apply, among others.Moreover, during the last 4 years the Spanish Program: Impact genomics has provided WGS for more than 2,000 Rare Diseases patients, including some with IRD, to explore the feasibility to implement WGS in NHS.In the Department of Clinical Genetics of Fundacion Jimenez Diaz, Madrid, we have integrated in these national programs, as well as have introduced through research projects, the use of long reads WGS for IRD characterization.As a result, we show the results of the cases studied in our centre. By March 2024, 6,025 unrelated affected IRD families had been recorded, 5,123 of them could be genetically studied, comprising around 8,000 cases. The families were distributed into 3 categories: Non syndromic Retinitis Pigmentosa (RP) (2,597 families; 60% characterized), Syndromic RP (651 families; 69% characterized), and NonRP (Macular Dystrophies, Cone Dystrophies, Cone Rod Dystrophies, etc) (1,875 families; 63% characterized)In our cohort, the largest in the world from one single centre, 192 different genes were found as responsible for IRD, and about of 2,000 different causative variants were identified, half of them present in only one family. Despite this huge genetic heterogeneity, one fourth of the characterised families showed involvement of only seven genes (ABCA4, USH2A, RPGR, CRB1, RS1, PRPH2, and BEST1). RPE65 gene biallelic pathogenic variants were present in 30 families (around 50 affected cases).This approach has allowed to implement not only the molecular characterization, but also to offer authorized treatment (Luxturna) for more than 30 Spanish cases in 6 centres and access to reproductive counselling and techniques, as PGT for severe IRD conditions.