2026-04-29T04:10:09Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/252742024-10-23T13:07:22Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16958

00925njm 22002777a 4500 dc Martín-Sánchez, Marta author Bravo-Gil, Nereida author González-Del Pozo, María author Méndez-Vidal, Cristina author Fernández-Suárez, Elena author Rodríguez-de la Rúa, Enrique author Borrego, Salud author Antiñolo, Guillermo author 2020-12-08 The management of unsolved inherited retinal dystrophies (IRD) cases is challenging since no standard pipelines have been established. This study aimed to define a diagnostic algorithm useful for the diagnostic routine and to address unsolved cases. Here, we applied a Next-Generation Sequencing-based workflow, including a first step of panel sequencing (PS) followed by clinical-exome sequencing (CES) and whole-exome sequencing (WES), in 46 IRD patients belonging to 42 families. Twenty-six likely causal variants in retinal genes were found by PS and CES. CES and WES allowed proposing two novel candidate loci (WDFY3 and a X-linked region including CITED1), both abundantly expressed in human retina according to RT-PCR and immunohistochemistry. After comparison studies, PS showed the best quality and cost values, CES and WES involved similar analytical efforts and WES presented the highest diagnostic yield. These results reinforce the relevance of panels as a first step in the diagnostic routine and suggest WES as the next strategy for unsolved cases, reserving CES for the simultaneous study of multiple conditions. Standardizing this algorithm would enhance the efficiency and equity of clinical genetics practice. Furthermore, the identified candidate genes could contribute to increase the diagnostic yield and expand the mutational spectrum in these disorders. http://hdl.handle.net/10668/16770 https://hdl.handle.net/20.500.12105/25274 33302505 10.3390/ijms21249355 1422-0067 International journal of molecular sciences CITED1 WDFY3 Genetic diagnosis Inherited retinal dystrophies Next generation sequencing A Multi-Strategy Sequencing Workflow in Inherited Retinal Dystrophies: Routine Diagnosis, Addressing Unsolved Cases and Candidate Genes Identification.