Publication Date
1-1-2021
Journal
Frontiers in Genetics
DOI
10.3389/fgene.2021.647400
PMID
33737949
PMCID
PMC7960924
PubMedCentral® Posted Date
3-2-2021
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
inherited retinal dystrophies, whole-genome sequencing, splicing, deep-intronic mutations, minigenes
Abstract
High throughput sequencing technologies have revolutionized the identification of mutations responsible for a diverse set of Mendelian disorders, including inherited retinal disorders (IRDs). However, the causal mutations remain elusive for a significant proportion of patients. This may be partially due to pathogenic mutations located in non-coding regions, which are largely missed by capture sequencing targeting the coding regions. The advent of whole-genome sequencing (WGS) allows us to systematically detect non-coding variations. However, the interpretation of these variations remains a significant bottleneck. In this study, we investigated the contribution of deep-intronic splice variants to IRDs. WGS was performed for a cohort of 571 IRD patients who lack a confident molecular diagnosis, and potential deep intronic variants that affect proper splicing were identified using SpliceAI. A total of six deleterious deep intronic variants were identified in eight patients. An
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