ArticleThe Journal of investigative dermatology2013
Premature termination codon read-through in the ABCC6 gene: potential treatment for pseudoxanthoma elasticum.
Article in The Journal of investigative dermatology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Ataluren treatment of patients with nonsense mutation dystrophinopathy.Muscle & nerve · 2014Trial
- [Pseudoxanthoma elasticum: the dermatologist as a guide].Dermatologie (Heidelberg, Germany) · 2022Article
- Nonsense Suppression Therapy: An Emerging Treatment for Hereditary Skin Diseases.Acta dermato-venereologica · 2022Review
- Review
- Ataluren-Promising Therapeutic Premature Termination Codon Readthrough Frontrunner.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Molecular Genetics and Modifier Genes in Pseudoxanthoma Elasticum, a Heritable Multisystem Ectopic Mineralization Disorder.The Journal of investigative dermatology · 2021Review
- ABCC6, Pyrophosphate and Ectopic Calcification: Therapeutic Solutions.International journal of molecular sciences · 2021Review
- Therapeutics Development for Pseudoxanthoma Elasticum and Related Ectopic Mineralization Disorders: Update 2020.Journal of clinical medicine · 2020Review
- Reply to Van Gils and Vanakker.The Journal of investigative dermatology · 2019Article
- Adenovirus-Mediated ABCC6 Gene Therapy for Heritable Ectopic Mineralization Disorders.The Journal of investigative dermatology · 2019Article
- PXE, a Mysterious Inborn Error Clarified.Trends in biochemical sciences · 2019Review
- Use of PTC124 for nonsense suppression therapy targeting BMP4 nonsense variants in vitro and the bmp4st72 allele in zebrafish.PloS one · 2019Article
- Pyrophosphate Supplementation Prevents Chronic and Acute Calcification in ABCC6-Deficient Mice.The American journal of pathology · 2017Article
- Pseudoxanthoma elasticum.Orphanet journal of rare diseases · 2017Review
- Insights into Pathomechanisms and Treatment Development in Heritable Ectopic Mineralization Disorders: Summary of the PXE International Biennial Research Symposium-2016.The Journal of investigative dermatology · 2017Review
- Functional Rescue of ABCC6 Deficiency by 4-Phenylbutyrate Therapy Reduces Dystrophic Calcification in Abcc6The Journal of investigative dermatology · 2017Article
- Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Research Progress in Pseudoxanthoma Elasticum and Related Ectopic Mineralization Disorders.The Journal of investigative dermatology · 2016Review
- CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis.Frontiers in pharmacology · 2016Review
- Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment.Intractable & rare diseases research · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder manifesting with ectopic connective tissue mineralization, caused by mutations in the ABCC6 gene, with ~35% of all mutations being premature termination mutations. In this study, we investigated the therapeutic potential of the nonsense codon read-through-inducing drug, PTC124, in treating PXE. The ability of this drug to facilitate read-through of nonsense mutations was examined in HEK293 cells transfected with human ABCC6 expression constructs harboring seven different PXE-associated nonsense mutations, and was evaluated by immunofluorescence and In-Cell ELISA. Our data demonstrated that PTC124 did not exhibit cytotoxicity in concentrations up to 20 μg ml(-1), and the facilitated read-through varied not only with dose but also with sequence context. Considering the redundancy of the genetic code, it was postulated that in case of the most common recurrent nonsense mutation, p.R1141X, the read-through may result in substitution of the arginine 1,141 by glycine, tryptophan, or cysteine. Their potential pathogenicity was tested in a recently developed zebrafish messenger RNA (mRNA) rescue assay, and demonstrated that all three mRNA transcripts were able to rescue abcc6a morpholino-induced phenotype of zebrafish. Thus, our results suggest that read-through of nonsense mutations in ABCC6 by PTC124 may have potential for pharmacologic treatment of PXE.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.