ArticleThe Journal of clinical investigation2001
Uroporphyrinogen III synthase erythroid promoter mutations in adjacent GATA1 and CP2 elements cause congenital erythropoietic porphyria.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 94 citations in OpenAlex.
- Identification of a novel nonsense mutation and a recurrent missense mutation in UROS gene in a patient with congenital erythropoietic porphyria.Frontiers in genetics · 2025Article
- TFCP2 as a therapeutic nexus: unveiling molecular signatures in cancer.Cancer metastasis reviews · 2024Review
- Functional categorization of gene regulatory variants that cause Mendelian conditions.Human genetics · 2024Review
- Severe Perinatal Presentations of Günther's Disease: Series of 20 Cases and Perspectives.Life (Basel, Switzerland) · 2024Article
- Acquired erythropoietic uroporphyria associated with clonal cytopenia of undetermined significance.JAAD case reports · 2023Article
- SUMOylation-mediated PSME3-20Science advances · 2023Article
- Epigenetic and Transcriptional Control of Erythropoiesis.Frontiers in genetics · 2022Review
- Article
- Porphyrias in the Age of Targeted Therapies.Diagnostics (Basel, Switzerland) · 2021Review
- X-linked dominant protoporphyria in a Chinese pedigree reveals a four-based deletion ofAnnals of translational medicine · 2020Article
- GATA1 mutations in red cell disorders.IUBMB life · 2020Review
- Congenital erythropoietic porphyria: Recent advances.Molecular genetics and metabolism · 2019Review
- Recent advances on porphyria genetics: Inheritance, penetrance & molecular heterogeneity, including new modifying/causative genes.Molecular genetics and metabolism · 2019Review
- The Pleiotropic Effects of GATA1 and KLF1 in Physiological Erythropoiesis and in Dyserythropoietic Disorders.Frontiers in physiology · 2019Review
- The molecular genetic background leading to the formation of the human erythroid-specific XgBlood advances · 2018Article
- Mbd2-CP2c loop drives adult-type globin gene expression and definitive erythropoiesis.Nucleic acids research · 2018Article
- Concise Review: Epigenetic Regulation of Hematopoiesis: Biological Insights and Therapeutic Applications.Stem cells translational medicine · 2017Review
- Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits.Cell · 2016Article
- Insight into GATA1 transcriptional activity through interrogation of cis elements disrupted in human erythroid disorders.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Society for Pediatric Research 2015 Young Investigator Award: genetics of human hematopoiesis-what patients can teach us about blood cell production.Pediatric research · 2016Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Congenital erythropoietic porphyria, an autosomal recessive inborn error of heme biosynthesis, results from the markedly deficient activity of uroporphyrinogen III synthase. Extensive mutation analyses of 40 unrelated patients only identified approximately 90% of mutant alleles. Sequencing the recently discovered erythroid-specific promoter in six patients with a single undefined allele identified four novel mutations clustered in a 20-bp region: (a) a -70T to C transition in a putative GATA-1 consensus binding element, (b) a -76G to A transition, (c) a -86C to A transversion in three unrelated patients, and (d) a -90C to A transversion in a putative CP2 binding motif. Also, a -224T to C polymorphism was present in approximately 4% of 200 unrelated Caucasian alleles. We inserted these mutant sequences into luciferase reporter constructs. When transfected into K562 erythroid cells, these constructs yielded 3 +/- 1, 54 +/- 3, 43 +/- 6, and 8 +/- 1%, respectively, of the reporter activity conferred by the wild-type promoter. Electrophoretic mobility shift assays indicated that the -70C mutation altered GATA1 binding, whereas the adjacent -76A mutation did not. Similarly, the -90C mutation altered CP2 binding, whereas the -86A mutation did not. Thus, these four pathogenic erythroid promoter mutations impaired erythroid-specific transcription, caused CEP, and identified functionally important GATA1 and CP2 transcriptional binding elements for erythroid-specific heme biosynthesis.
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