RT Journal Article
T1 A Multi-Strategy Sequencing Workflow in Inherited Retinal Dystrophies: Routine Diagnosis, Addressing Unsolved Cases and Candidate Genes Identification.
A1 Martin-Sanchez, Marta
A1 Bravo-Gil, Nereida
A1 Gonzalez-Del-Pozo, Maria
A1 Mendez-Vidal, Cristina
A1 Fernandez-Suarez, Elena
A1 Rodriguez-de-la-Rua, Enrique
A1 Borrego, Salud
A1 Antiñolo, Guillermo
K1 CITED1
K1 WDFY3
K1 genetic diagnosis
K1 inherited retinal dystrophies
K1 next generation sequencing
AB 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.
PB MDPI AG
YR 2020
FD 2020-12-08
LK http://hdl.handle.net/10668/16770
UL http://hdl.handle.net/10668/16770
LA en
NO Martín-Sánchez M, Bravo-Gil N, González-Del Pozo M, Méndez-Vidal C, Fernández-Suárez E, Rodríguez-de la Rúa E, et al.  A Multi-Strategy Sequencing Workflow in Inherited Retinal Dystrophies: Routine Diagnosis, Addressing Unsolved Cases and Candidate Genes Identification. Int J Mol Sci. 2020 Dec 8;21(24):9355.
DS RISalud
RD Apr 11, 2025