A Multi-Strategy Sequencing Workflow in Inherited Retinal Dystrophies: Routine Diagnosis, Addressing Unsolved Cases and Candidate Genes Identification

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Dec 11

PMID 33302505

Citations 5

Authors

Marta Martin-Sanchez

Nereida Bravo-Gil

Maria Gonzalez-Del Pozo

Cristina Mendez-Vidal

Elena Fernandez-Suarez

Enrique Rodriguez-de la Rua

Salud Borrego

Guillermo Antinolo

Affiliations

Soon will be listed here.

Abstract

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 ( and a X-linked region including ), 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.

Citing Articles

A genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice.

Mendez-Vidal C, Bravo-Gil N, Perez-Florido J, Marcos-Luque I, Fernandez R, Fernandez-Rueda J J Transl Med. 2025; 23(1):86.

PMID: 39833864 PMC: 11748347. DOI: 10.1186/s12967-025-06069-2.

Long-read sequencing improves the genetic diagnosis of retinitis pigmentosa by identifying an Alu retrotransposon insertion in the EYS gene.

Fernandez-Suarez E, Gonzalez-Del Pozo M, Mendez-Vidal C, Martin-Sanchez M, Mena M, de la Morena-Barrio B Mob DNA. 2024; 15(1):9.

PMID: 38704576 PMC: 11069205. DOI: 10.1186/s13100-024-00320-1.

Expanding the phenotype of : a range of macular dystrophies as the major clinical manifestations in patients with a dominant splicing variant.

Fernandez-Suarez E, Gonzalez-Del Pozo M, Garcia-Nunez A, Mendez-Vidal C, Martin-Sanchez M, Mejias-Carrasco J Front Cell Dev Biol. 2023; 11:1197744.

PMID: 37547476 PMC: 10401274. DOI: 10.3389/fcell.2023.1197744.

Rare variant analyses across multiethnic cohorts identify novel genes for refractive error.

Musolf A, Haarman A, Luben R, Ong J, Patasova K, Trapero R Commun Biol. 2023; 6(1):6.

PMID: 36596879 PMC: 9810640. DOI: 10.1038/s42003-022-04323-7.

Inherited Retinal Diseases.

Ben-Yosef T Int J Mol Sci. 2022; 23(21).

PMID: 36362249 PMC: 9654499. DOI: 10.3390/ijms232113467.

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