ArticleProceedings of the National Academy of Sciences of the United States of America2003
Primary hyperoxaluria type 1 in the Canary Islands: a conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00283387 (Efficacy of Betaine for Reduction of Urine Oxalate in Patients With Type 1 Primary Hyperoxaluria), which is not on this map. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Efficacy of Betaine for Reduction of Urine Oxalate in Patients With Type 1 Primary Hyperoxaluria
Who cites it
41 citing papers in PubMed, 127 citations in OpenAlex.
- Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice.Clinical journal of the American Society of Nephrology : CJASN · 2014Trial
- Clinical and molecular spectrum of primary hyperoxaluria type 1 in Tunisia: pediatric presentation and minimum observed prevalence.Pediatric nephrology (Berlin, Germany) · 2026Article
- Expanding CIRdb, a comprehensive catalog of whole-exome sequencing data of Canary Islanders.iScience · 2026Article
- Does HLA explain the high incidence of childhood-onset type 1 diabetes in the Canary Islands? The role of Asp57 DQB1 molecules.BMC pediatrics · 2024Article
- Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs.Biomolecules · 2024Review
- Restored glyoxylate metabolism after AGXT gene correction and direct reprogramming of primary hyperoxaluria type 1 fibroblasts.iScience · 2024Article
- Determinants of Kidney Failure in Primary Hyperoxaluria Type 1: Findings of the European Hyperoxaluria Consortium.Kidney international reports · 2023Article
- Phosphorylation of Thr9 Affects the Folding Landscape of the N-Terminal Segment of Human AGT Enhancing Protein Aggregation of Disease-Causing Mutants.Molecules (Basel, Switzerland) · 2022Article
- Clinical and molecular characterization of primary hyperoxaluria in Egypt.Scientific reports · 2022Article
- Identification of Human Alanine-Glyoxylate Aminotransferase Ligands as Pharmacological Chaperones for Variants Associated with Primary Hyperoxaluria Type 1.Journal of medicinal chemistry · 2022Article
- Primary hyperoxaluria type 1: pathophysiology and genetics.Clinical kidney journal · 2022Review
- Perspectives in primary hyperoxaluria - historical, current and future clinical interventions.Nature reviews. Urology · 2022Review
- A new era of treatment for primary hyperoxaluria type 1.Nature reviews. Nephrology · 2021Article
- Small Molecule-Based Enzyme Inhibitors in the Treatment of Primary Hyperoxalurias.Journal of personalized medicine · 2021Review
- Human MiR-4660 regulates the expression of alanine-glyoxylate aminotransferase and may be a biomarker for idiopathic oxalosis.Clinical and experimental nephrology · 2019Article
- Genomic Analyses of Human European Diversity at the Southwestern Edge: Isolation, African Influence and Disease Associations in the Canary Islands.Molecular biology and evolution · 2018Article
- Review
- Identification of compound heterozygous patients with primary hyperoxaluria type 1: clinical evaluations and in silico investigations.BMC nephrology · 2017Article
- Identification of Small Molecule Compounds for Pharmacological Chaperone Therapy of Aspartylglucosaminuria.Scientific reports · 2016Article
- High throughput cell-based assay for identification of glycolate oxidase inhibitors as a potential treatment for Primary Hyperoxaluria Type 1.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary hyperoxaluria type 1 (PH1) is an inborn error of metabolism resulting from a deficiency of alanine:glyoxylate aminotransferase (AGXT; EC 2.6.1.44). Most of the PH1 alleles detected in the Canary Islands carry the Ile-244 --> Thr (I244T) mutation in the AGXT gene, with 14 of 16 patients homozygous for this mutation. Four polymorphisms within AGXT and regional microsatellites also were shared in their haplotypes (AGXT*LTM), consistent with a founder effect. The consequences of these amino acid changes were investigated. Although I244T alone did not affect AGXT activity or subcellular localization, when present in the same protein molecule as Leu-11 --> Pro (L11P), it resulted in loss of enzymatic activity in soluble cell extracts. Like its normal counterpart, the AGXT*LTM protein was present in the peroxisomes but it was insoluble in detergent-free buffers. The polymorphism L11P behaved as an intragenic modifier of the I244T mutation, with the resulting protein undergoing stable interaction with molecular chaperones and aggregation. This aggregation was temperature-sensitive. AGXT*LTM expressed in Escherichia coli, as a GST-fusion protein, and in insect cells could be purified and retained enzymatic activity. Among various chemical chaperones tested in cell culture, betaine substantially improved the solubility of the mutant protein and the enzymatic activity in cell lysates. In summary, I244T, the second most common mutation responsible for PH1, is a protein conformational disease that may benefit from new therapies with pharmacological chaperones or small molecules to minimize protein aggregation.
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