ArticleHuman molecular genetics2012
Deep intronic mutation in OFD1, identified by targeted genomic next-generation sequencing, causes a severe form of X-linked retinitis pigmentosa (RP23).
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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101 citing papers in PubMed, 152 citations in OpenAlex.
- Identification of a novel heterozygous missense mutation in the CACNA1F gene in a chinese family with retinitis pigmentosa by next generation sequencing.BioMed research international · 2015Trial
- Ciliary Defects in Inherited Retinal Diseases.Advanced genetics (Hoboken, N.J.) · 2026Review
- Alternative Splicing Dysregulation in Retinitis Pigmentosa: Pathogenic Mechanisms and Therapeutic Opportunities.Biomolecules · 2025Review
- New genetic diagnoses for inherited retinal dystrophies by integrating splicing tools into NGS pipelines.NPJ genomic medicine · 2025Article
- Analysis of choriocapillaris vascular density in patients with retinitis pigmentosa caused by RPGR gene mutations.BMC ophthalmology · 2025Article
- Unveiling the Genetic and Phenotypic Landscape of a Chinese Cohort With Retinitis Pigmentosa.Molecular genetics & genomic medicine · 2025Article
- Pathogenic cryptic variants detectable through exome data reanalysis significantly increase the diagnostic yield in Joubert syndrome.European journal of human genetics : EJHG · 2025Article
- Article
- Exploring non-coding variants and evaluation of antisense oligonucleotides for splicing redirection in Usher syndrome.Molecular therapy. Nucleic acids · 2024Article
- Screening of Inherited Retinal Disease Patients in a Low-Resource Setting Using an Augmented Next-Generation Sequencing Panel.Molecular genetics & genomic medicine · 2024Article
- Review
- Alternative RNA Splicing in the Retina: Insights and Perspectives.Cold Spring Harbor perspectives in medicine · 2023Review
- Asymmetric presentation with a novel RP2 gene mutation in X-Linked retinitis pigmentosa: a case report.BMC ophthalmology · 2023Article
- Cellular and Molecular Mechanisms of Pathogenesis Underlying Inherited Retinal Dystrophies.Biomolecules · 2023Review
- Article
- Retinal Degeneration Animal Models in Bardet-Biedl Syndrome and Related Ciliopathies.Cold Spring Harbor perspectives in medicine · 2023Review
- Review
- Non-syndromic Retinal Degeneration Caused by Pathogenic Variants in Joubert Syndrome Genes.Advances in experimental medicine and biology · 2023Article
- Genetic dissection of non-syndromic retinitis pigmentosa.Indian journal of ophthalmology · 2022Review
- Expanding the phenotype of males with OFD1 pathogenic variants-a case report and literature review.European journal of medical genetics · 2022Article
41 more citing papers are in PubMed but not listed here.
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16 authors at 1 institution in 1 country.
Funding
Abstract
X-linked retinitis pigmentosa (XLRP) is genetically heterogeneous with two causative genes identified, RPGR and RP2. We previously mapped a locus for a severe form of XLRP, RP23, to a 10.71 Mb interval on Xp22.31-22.13 containing 62 genes. Candidate gene screening failed to identify a causative mutation, so we adopted targeted genomic next-generation sequencing of the disease interval to determine the molecular cause of RP23. No coding variants or variants within or near splice sites were identified. In contrast, a variant deep within intron 9 of OFD1 increased the splice site prediction score 4 bp upstream of the variant. Mutations in OFD1 cause the syndromic ciliopathies orofaciodigital syndrome-1, which is male lethal, Simpson-Golabi-Behmel syndrome type 2 and Joubert syndrome. We tested the effect of the IVS9+706A>G variant on OFD1 splicing in vivo. In RP23 patient-derived RNA, we detected an OFD1 transcript with the insertion of a cryptic exon spliced between exons 9 and 10 causing a frameshift, p.N313fs.X330. Correctly spliced OFD1 was also detected in patient-derived RNA, although at reduced levels (39%), hence the mutation is not male lethal. Our data suggest that photoreceptors are uniquely susceptible to reduced expression of OFD1 and that an alternative disease mechanism can cause XLRP. This disease mechanism of reduced expression for a syndromic ciliopathy gene causing isolated retinal degeneration is reminiscent of CEP290 intronic mutations that cause Leber congenital amaurosis, and we speculate that reduced dosage of correctly spliced ciliopathy genes may be a common disease mechanism in retinal degenerations.
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