ArticleMolecular genetics & genomic medicine2019
The identification of a RNA splice variant in TULP1 in two siblings with early-onset photoreceptor dystrophy.
Article in Molecular genetics & genomic medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 18 citations in OpenAlex.
- Efficacy, biodistribution and safety comparison of chemically modified antisense oligonucleotides in the retina.Nucleic acids research · 2024Article
- Biallelic Variants in TULP1 Are Associated with Heterogeneous Phenotypes of Retinal Dystrophy.International journal of molecular sciences · 2023Article
- A novel homozygous TUB mutation associated with autosomal recessive retinitis pigmentosa in a consanguineous Chinese family.BMC medical genomics · 2023Article
- Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis.Frontiers in cell and developmental biology · 2023Article
- Tulp1 deficiency causes early-onset retinal degeneration through affecting ciliogenesis and activating ferroptosis in zebrafish.Cell death & disease · 2022Article
- Identification of a Complex Allele in IMPG2 as a Cause of Adult-Onset Vitelliform Macular Dystrophy.Investigative ophthalmology & visual science · 2022Article
- Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing.International journal of molecular sciences · 2022Article
- Whole genome sequencing and in vitro splice assays reveal genetic causes for inherited retinal diseases.NPJ genomic medicine · 2021Article
- Next-Generation Sequencing Applications for Inherited Retinal Diseases.International journal of molecular sciences · 2021Review
- Spectrum of splicing variants in disease genes and the ability of RNA analysis to reduce uncertainty in clinical interpretation.American journal of human genetics · 2021Article
- Findings from a Genotyping Study of Over 1000 People with Inherited Retinal Disorders in Ireland.Genes · 2020Article
- The identification of a RNA splice variant in TULP1 in two siblings with early-onset photoreceptor dystrophy.Molecular genetics & genomic medicine · 2019Article
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8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundEarly-onset photoreceptor dystrophies are a major cause of irreversible visual impairment in children and young adults. This clinically heterogeneous group of disorders can be caused by mutations in many genes. Nevertheless, to date, 30%-40% of cases remain genetically unexplained. In view of expanding therapeutic options, it is essential to obtain a molecular diagnosis in these patients as well. In this study, we aimed to identify the genetic cause in two siblings with genetically unexplained retinal disease.
methodsWhole exome sequencing was performed to identify the causative variants in two siblings in whom a single pathogenic variant in TULP1 was found previously. Patients were clinically evaluated, including assessment of the medical history, slit-lamp biomicroscopy, and ophthalmoscopy. In addition, a functional analysis of the putative splice variant in TULP1 was performed using a midigene assay.
resultsClinical assessment showed a typical early-onset photoreceptor dystrophy in both the patients. Whole exome sequencing identified two pathogenic variants in TULP1, a c.1445G>A (p.(Arg482Gln)) missense mutation and an intronic c.718+23G>A variant. Segregation analysis confirmed that both siblings were compound heterozygous for the TULP1 c.718+23G>A and c.1445G>A variants, while the unaffected parents were heterozygous. The midigene assay for the c.718+23G>A variant confirmed an elongation of exon 7 leading to a frameshift.
conclusionHere, we report the first near-exon RNA splice variant that is not present in a consensus splice site sequence in TULP1, which was found in a compound heterozygous manner with a previously described pathogenic TULP1 variant in two patients with an early-onset photoreceptor dystrophy. We provide proof of pathogenicity for this splice variant by performing an in vitro midigene splice assay, and highlight the importance of analysis of noncoding regions beyond the noncanonical splice sites in patients with inherited retinal diseases.
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