Dataset Information

The Application of Next-Generation Sequencing (NGS) in Neonatal-Onset Urea Cycle Disorders (UCDs): Clinical Course, Metabolomic Profiling, and Genetic Findings in Nine Chinese Hyperammonemia Patients.

ABSTRACT: During Jan. 2016-Dec. 2019, nine Chinese patients from eight unrelated families were diagnosed with neonatal-onset UCDs by targeted panel sequencing or whole-exome sequencing (WES). Their clinical manifestations, biochemical features, 180-day-age outcomes, and molecular genetic characteristics were reviewed retrospectively. NGS-based tests revealed 7 patients diagnosed with ornithine transcarbamylase deficiency (OTCD) and 2 with carbamoylphosphate synthetase I deficiency (CPS1D). The spectrum of the clinical presentation of nine affected individuals progressed from unspecific symptoms like poor feeding to somnolence, coma, and death. All patients presented with an acute hyperammonemia. The most robust metabolic pattern in OTCD was hyperglutaminemic hyperammonemia with high concentration of urine orotic acid, and it was reported in six patients. Of ten variants found on the OTC gene and CPS1 gene, 3 were novel: (c.176T>C (p.L59P)) in the OTC gene, c.2938G>A (p.G980S) and c.3734T>A (p.L1245H) in the CPS1 gene. There was a high mortality rate of 77.78% (7/9) for all the defects combined. An OTC-deficient male and a CPS1-deficient female survived from episodes of hyperammonemia. Although prompt recognition of UCD and the use of alternative pathway therapy in addition to provision of appropriate nutrition and dialysis improved survival, the overall outcomes for the neonatal-onset type are poor in China.

SUBMITTER: Zhou Q

PROVIDER: S-EPMC7479453 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Application of Next-Generation Sequencing (NGS) in Neonatal-Onset Urea Cycle Disorders (UCDs): Clinical Course, Metabolomic Profiling, and Genetic Findings in Nine Chinese Hyperammonemia Patients.

Zhou Qingnv Q Huang Huafei H Ma Li L Zhu Tianwen T

BioMed research international 20200831

During Jan. 2016-Dec. 2019, nine Chinese patients from eight unrelated families were diagnosed with neonatal-onset UCDs by targeted panel sequencing or whole-exome sequencing (WES). Their clinical manifestations, biochemical features, 180-day-age outcomes, and molecular genetic characteristics were reviewed retrospectively. NGS-based tests revealed 7 patients diagnosed with ornithine transcarbamylase deficiency (OTCD) and 2 with carbamoylphosphate synthetase I deficiency (CPS1D). The spectrum of ...[more]

PMID: 32934962

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Project description:Plant nutrition takes advantage by the simultaneous presence of more N forms in the rhizosphere. In the last decades the interplay between ammonium and nitrate acquisition systems in roots has been deeply investigated. Although widely used as fertilizers, the occurrence of cross connection between urea and ammonium nutrition has been scarcely studied in plants, especially at molecular level. In a recent paper we provided evidence that maize plants fed with urea and ammonium mix showed a better N-uptake efficiency than plants fed with ammonium or urea alone. To elucidate the molecular mechanism underlying this response, transcriptomic and metabolomic changes occurring in maize plants were investigated. Transcriptomic analyses indicated that several transporters and enzymes involved in N-nutrition were found upregulated by all three N-treatments (AMT1.3, NRT1.1, NRT2.1, GS1, GOGAT, GDH), confirming that urea is a direct source of N for plants. Depending on N-form available in nutrient solution a peculiar response at transcriptomic and metabolomic level was observed, especially after 24 hours of treatment. In comparison to one single N-form, urea and ammonium mix induced a prompt assimilation of N, characterized by an overaccumulation of main amino acids in shoots, and an upregulation of ZmAMT1.1. Moreover even a peculiar modulation of aquaporins, carbonic anydrases, glutamine synthetase, amino aspartate, as well as the glycolysis-TCA cycle was induced in roots by urea and ammonium mix. Depending on N-form available in the external media, even changes in phytohormone’s composition were observed in maize (CKs, ABA, JA); in particular, already after 24 hours of treatment, urea induced the accumulation of trans-zeatin in shoots. Through a multiomics approach, we provide for the first time molecular characterization of maize response to urea and ammonium nutrition. This study paves the way to formulate guidelines for the optimization of N fertilization of crops to improve the N use efficiency in plants and therefore limit N losses in the environment.

Dataset Information

The Application of Next-Generation Sequencing (NGS) in Neonatal-Onset Urea Cycle Disorders (UCDs): Clinical Course, Metabolomic Profiling, and Genetic Findings in Nine Chinese Hyperammonemia Patients.

Publications

The Application of Next-Generation Sequencing (NGS) in Neonatal-Onset Urea Cycle Disorders (UCDs): Clinical Course, Metabolomic Profiling, and Genetic Findings in Nine Chinese Hyperammonemia Patients.

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