AI Article Synopsis
- The study focused on validating genetic variants found in inherited retinal dystrophy (IRD) patients located in non-canonical splice sites (NCSS).
- After analyzing samples through next-generation sequencing, the researchers identified and prioritized NCSS variants, confirming their pathogenic nature through functional tests.
- Four novel NCSS variants were discovered, causing various splicing issues that impact gene function, ultimately enhancing genetic diagnosis for IRD patients and paving the way for potential gene therapies.
Article Abstract
Aims: We aimed to validate the pathogenicity of genetic variants identified in inherited retinal dystrophy (IRD) patients, which were located in non-canonical splice sites (NCSS).
Methods: After next generation sequencing (NGS) analysis (target gene panels or whole exome sequencing (WES)), NCSS variants were prioritized according to predictions. and functional tests were used to validate their pathogenicity.
Results: Four novel NCSS variants have been identified. They are located in intron 33 and 34 of (c.4774-9G>A and c.4849-8C>G, respectively), intron 2 of (c.101-3T>G) and intron 3 of (c.884-14G>A). Functional analysis detected different aberrant splicing events, including intron retention, exon skipping and intronic nucleotide addition, whose molecular effect was either the disruption or the elongation of the open reading frame of the corresponding gene.
Conclusions: Our data increase the genetic diagnostic yield of IRD patients and expand the landscape of pathogenic variants, which will have an impact on the genotype-phenotype correlations and allow patients to opt for the emerging gene and cell therapies.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231145 | PMC |
| http://dx.doi.org/10.3390/genes11040378 | DOI Listing |
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