Targeted long-read cDNA sequencing reveals novel splice-altering pathogenic variants causing retinal dystrophies.

ABSTRACT: Splice-altering variants are suggested to be responsible for part of the missing heritability of inherited retinal diseases (IRDs). The interpretation of these variants is challenging as functional evidence is required to validate pathogenicity. We explored the diagnostic value of a targeted long-read cDNA sequencing (lrcDNA-seq) approach to investigate IRD-associated splicing defects. For each affected individual, RNA was isolated from blood, and for each candidate gene, cDNA amplicons, spanning the complete open reading frame or multiple exons, were generated and subjected to long-read sequencing. We validated our approach by assessing previously described pathogenic splice-altering variants in IRD-associated genes. Next, we investigated six genetically unexplained affected individuals,

SUBMITTER: Capasso D 

PROVIDER: S-EPMC12099450 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature