ArticleNPJ genomic medicine2021
Whole genome sequencing and in vitro splice assays reveal genetic causes for inherited retinal diseases.
Article in NPJ genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- Review
- Genetic Testing in Inherited Retinal Disease: Current Strategies and Future Directions.Journal of personalized medicine · 2026Review
- A novel phenotype-guided genome analysis pipeline for variant discovery.NPJ genomic medicine · 2026Article
- Loss-of-function variants in SAXO6, encoding a microtubule inner protein of photoreceptor cilia, cause a late-onset retinal dystrophy.American journal of human genetics · 2026Article
- Enhancing Molecular Diagnostic Accuracy in Genetic Eye Disorders Through a Personalized Re-Evaluation Strategy.Investigative ophthalmology & visual science · 2026Article
- The landscape of variants in pre-mRNA-processing factor genes in an Irish cohort.Genetics in medicine open · 2026Article
- Decoding structural birth defects through genomic landscapes: Innovative frameworks for diagnosis (Review).International journal of molecular medicine · 2026Review
- Personalised genomic strategies improve diagnostic yield in inherited retinal dystrophies: a stepwise, patient-centred approach.Eye (London, England) · 2025Article
- Hidden Splicing Variants in Inherited Retinal Degeneration: Discovery and Functional Insight.Investigative ophthalmology & visual science · 2025Article
- Article
- Long-read technologies identify a hidden LINE-1/ERV1 insertion in IQCB1 as causative variant for Senior-Løken syndrome.NPJ genomic medicine · 2025Article
- Systematic genetic assessment of hearing loss using whole-genome sequencing identifies pathogenic variants.Experimental & molecular medicine · 2025Article
- Genetics and diagnostics of inherited retinal diseases in the era of whole genome sequencing.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Novel Splice-Altering Variants in theGenes · 2024Article
- Exploring non-coding variants and evaluation of antisense oligonucleotides for splicing redirection in Usher syndrome.Molecular therapy. Nucleic acids · 2024Article
- Coding and non-coding variants in the ciliopathy gene CFAP410 cause early-onset non-syndromic retinal degeneration.NPJ genomic medicine · 2024Article
- Assessment of genes involved in lysosomal diseases using the ClinGen clinical validity framework.Molecular genetics and metabolism · 2024Article
- 18-Years of single-centre DNA testing in over 7000 index cases with inherited retinal dystrophies and optic neuropathies.Scientific reports · 2024Article
- Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach.Frontiers in genetics · 2024Article
- Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project.Journal of medical genetics · 2023Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
Abstract
Inherited retinal diseases (IRDs) are a major cause of visual impairment. These clinically heterogeneous disorders are caused by pathogenic variants in more than 270 genes. As 30-40% of cases remain genetically unexplained following conventional genetic testing, we aimed to obtain a genetic diagnosis in an IRD cohort in which the genetic cause was not found using whole-exome sequencing or targeted capture sequencing. We performed whole-genome sequencing (WGS) to identify causative variants in 100 unresolved cases. After initial prioritization, we performed an in-depth interrogation of all noncoding and structural variants in genes when one candidate variant was detected. In addition, functional analysis of putative splice-altering variants was performed using in vitro splice assays. We identified the genetic cause of the disease in 24 patients. Causative coding variants were observed in genes such as ATXN7, CEP78, EYS, FAM161A, and HGSNAT. Gene disrupting structural variants were also detected in ATXN7, PRPF31, and RPGRIP1. In 14 monoallelic cases, we prioritized candidate noncanonical splice sites or deep-intronic variants that were predicted to disrupt the splicing process based on in silico analyses. Of these, seven cases were resolved as they carried pathogenic splice defects. WGS is a powerful tool to identify causative variants residing outside coding regions or heterozygous structural variants. This approach was most efficient in cases with a distinct clinical diagnosis. In addition, in vitro splice assays provide important evidence of the pathogenicity of rare variants.
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Registered trials
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