ArticleHuman molecular genetics2015
Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis and decrease glycosylation precursors.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 83 citations in OpenAlex.
- Enhanced lactose utilization from milk enriched in Uridine-5'-monophosphate drives hepatic energy storage in young mammals.Food chemistry. Molecular sciences · 2026Article
- An Optimized Diagnostic Approach for Adults With Suspected Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Article
- Analysis of purines and pyrimidines across biospecimens: influence of storage temperature and duration.Scientific reports · 2026Article
- Phenotypic prediction of missense variants via deep contrastive learning.Nature biomedical engineering · 2026Article
- Epileptic encephalopathy in a young Bengal cat caused by CAD deficiency.Scientific reports · 2025Article
- Epileptic Encephalopathy Related to CAD Deleterious Variants-A Case Series.Diseases (Basel, Switzerland) · 2025Article
- A review of multiple diagnostic approaches in the undiagnosed diseases network to identify inherited metabolic diseases.Orphanet journal of rare diseases · 2024Review
- Novel CAD gene mutations in a boy with developmental and epileptic encephalopathy 50 with dramatic response to uridine therapy: a case report and a review of the literature.BMC pediatrics · 2024Review
- Evidence of synergistic mechanisms of hepatoprotective botanical herbal preparation ofFrontiers in pharmacology · 2024Article
- Beyond genetics: Deciphering the impact of missense variants in CAD deficiency.Journal of inherited metabolic disease · 2023Article
- A Tailored Strategy to Crosslink the Aspartate Transcarbamoylase Domain of the Multienzymatic Protein CAD.Molecules (Basel, Switzerland) · 2023Article
- Biomarker discovery in galactosemia: Metabolomics with UPLC/HRMS in dried blood spots.Frontiers in molecular biosciences · 2023Article
- Chemical Therapies for Congenital Disorders of Glycosylation.ACS chemical biology · 2022Review
- Inborn Errors of Nucleoside Transporter (NT)-Encoding Genes (International journal of molecular sciences · 2022Review
- Nutrition interventions in congenital disorders of glycosylation.Trends in molecular medicine · 2022Review
- Differential expression of enzymes in thymidylate biosynthesis in zebrafish at different developmental stages: implications for dtymk mutation-caused neurodegenerative disorders.BMC neuroscience · 2022Article
- CAD gene and early infantile epileptic encephalopathy-50; three Iranian deceased patients and a novel mutation: case report.BMC pediatrics · 2022Article
- Uridine monophosphate (UMP)-responsive developmental and epileptic encephalopathy: A case report of two siblings and a review of literature.Molecular genetics and metabolism reports · 2022Article
- Variant-specific effects define the phenotypic spectrum of HNRNPH2-associated neurodevelopmental disorders in males.Human genetics · 2022Article
- DTYMK is essential for genome integrity and neuronal survival.Acta neuropathologica · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
In mitochondria, carbamoyl-phosphate synthetase 1 activity produces carbamoyl phosphate for urea synthesis, and deficiency results in hyperammonemia. Cytoplasmic carbamoyl-phosphate synthetase 2, however, is part of a tri-functional enzyme encoded by CAD; no human disease has been attributed to this gene. The tri-functional enzyme contains carbamoyl-phosphate synthetase 2 (CPS2), aspartate transcarbamylase (ATCase) and dihydroorotase (DHOase) activities, which comprise the first three of six reactions required for de novo pyrimidine biosynthesis. Here we characterize an individual who is compound heterozygous for mutations in different domains of CAD. One mutation, c.1843-1G>A, results in an in-frame deletion of exon 13. The other, c.6071G>A, causes a missense mutation (p.Arg2024Gln) in a highly conserved residue that is essential for carbamoyl-phosphate binding. Metabolic flux studies showed impaired aspartate incorporation into RNA and DNA through the de novo synthesis pathway. In addition, CTP, UTP and nearly all UDP-activated sugars that serve as donors for glycosylation were decreased. Uridine supplementation rescued these abnormalities, suggesting a potential therapy for this new glycosylation disorder.
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