ArticleHuman mutation2018
Disease-causing mutations in the promoter and enhancer of the ornithine transcarbamylase gene.
Article in Human mutation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts.Nature communications · 2020Pooled it
- Mechanisms underlying disease-causing variants in promoters and enhancers.Nature genetics · 2026Review
- Article
- Multisite λ-Dynamics for Protein-DNA Binding Affinity Prediction.Journal of chemical theory and computation · 2025Article
- Article
- Datamining approaches for examining the low prevalence of N-acetylglutamate synthase deficiency and understanding transcriptional regulation of urea cycle genes.Journal of inherited metabolic disease · 2024Article
- Variant analysis and PGT-M of OTC gene in a Chinese family with ornithine carbamoyltransferase deficiency.BMC pregnancy and childbirth · 2024Article
- Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease.Orphanet journal of rare diseases · 2024Article
- Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency.Children (Basel, Switzerland) · 2023Review
- Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis.Cancer discovery · 2023Article
- Optimized high-throughput screening of non-coding variants identified from genome-wide association studies.Nucleic acids research · 2023Article
- Considerations for prenatal and postpartum management of a female patient with ornithine transcarbamylase deficiency.Molecular genetics and metabolism reports · 2022Article
- Challenges of managing ornithine transcarbamylase deficiency in female heterozygotes.Molecular genetics and metabolism reports · 2022Article
- Identification of Clinical Variants beyond the Exome in Inborn Errors of Metabolism.International journal of molecular sciences · 2022Article
- Ornithine transcarbamylase deficiency: A diagnostic odyssey.Journal of inherited metabolic disease · 2022Article
- A promoter variant in the OTC gene associated with late and variable age of onset hyperammonemia.Journal of inherited metabolic disease · 2022Article
- A serendipitous journey to a promoter variant: The c.-106C>A variant and its role in late-onset ornithine transcarbamylase deficiency.JIMD reports · 2022Article
- Intronic variants in inborn errors of metabolism: Beyond the exome.Frontiers in genetics · 2022Article
- Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review.Frontiers in genetics · 2022Article
- Extensive non-coding sequence divergence between the major human pathogenFrontiers in fungal biology · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
The ornithine transcarbamylase (OTC) gene is on the X chromosome and its product catalyzes the formation of citrulline from ornithine and carbamylphosphate in the urea cycle. About 10%-15% of patients, clinically diagnosed with OTC deficiency (OTCD), lack identifiable mutations in the coding region or splice junctions of the OTC gene on routine molecular testing. We collected DNA from such patients via retrospective review and by prospective enrollment. In nine of 38 subjects (24%), we identified a sequence variant in the OTC regulatory regions. Eight subjects had unique sequence variants in the OTC promoter and one subject had a novel sequence variant in the OTC enhancer. All sequence variants affect positions that are highly conserved in mammalian OTC genes. Functional studies revealed reduced reporter gene expression with all sequence variants. Two sequence variants caused decreased binding of the HNF4 transcription factor to its mutated binding site. Bioinformatic analyses combined with functional assays can be used to identify and authenticate pathogenic sequence variants in regulatory regions of the OTC gene, in other urea cycle disorders or other inborn errors of metabolism.
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