Integration of multigene panels for the diagnosis of hereditary retinal disorders using Next Generation Sequencing and bioinformatics approaches.

Di Resta C1,2, Spiga I3, Presi S3, Merella S3, Pipitone GB3, Manitto MP4, Querques G5, Parodi MB6, Ferrari M1,2,3, Carrera P2,3.

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Abstract

In recent years, Next-Generation Sequencing (NGS) opened a new way for the study of pathogenic mechanisms and for molecular diagnosis of inherited disorders. In the present work, we focused our attention on the inherited retinal dystrophies (IRDs), a group of specific disorders of the retina, displaying a very high clinical and genetic heterogeneity, whose genetic diagnosis is not easily feasible. It represents a paradigmatic example for the integration of clinical and molecular examination toward precision medicine. In this paper, we discuss the use of targeted NGS resequencing of selected gene panels in a cohort of patients affected by IRDs. We tested the hypothesis to apply a selective approach based on a careful clinical examination. By this approach we reached a 66% overall detection rate for pathogenic variants, with a 52% diagnostic yield. Reduction of the efforts for validation and classification of variants is a clear advantage for the management of genetictesting in a clinical setting.