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Meijer J, Nakajima Y, Zhang C, et al. Publisher's note. Identification of a novel synonymous mutation in the human β-ureidopropionase gene UPB1 affecting pre-mRNA splicing. Nucleosides Nucleotides Nucleic Acids. 2014;33(4):639-45doi: 10.1080/15257770.2014.913907.
Meijer, J., Nakajima, Y., Zhang, C., Meinsma, R., Ito, T., & Van Kuilenburg, A. B. (2014). Publisher's note. Identification of a novel synonymous mutation in the human β-ureidopropionase gene UPB1 affecting pre-mRNA splicing. Nucleosides, nucleotides & nucleic acids, 33(4), 639-45. https://doi.org/10.1080/15257770.2014.913907
Meijer, J, et al. "Publisher's note. Identification of a novel synonymous mutation in the human β-ureidopropionase gene UPB1 affecting pre-mRNA splicing." Nucleosides, nucleotides & nucleic acids vol. 33,4 (2014): 639-45. doi: https://doi.org/10.1080/15257770.2014.913907
Meijer J, Nakajima Y, Zhang C, Meinsma R, Ito T, Van Kuilenburg AB. Publisher's note. Identification of a novel synonymous mutation in the human β-ureidopropionase gene UPB1 affecting pre-mRNA splicing. Nucleosides Nucleotides Nucleic Acids. 2014;33(4):639-45. doi: 10.1080/15257770.2014.913907. PMID: 24940676.
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Nucleosides Nucleotides Nucleic Acids. 2014;33(4):639-45. doi: 10.1080/15257770.2014.913907.

Publisher's note. Identification of a novel synonymous mutation in the human β-ureidopropionase gene UPB1 affecting pre-mRNA splicing.

Nucleosides, nucleotides & nucleic acids

J Meijer, Y Nakajima, C Zhang, R Meinsma, T Ito, A B P Van Kuilenburg

PMID: 24940676 DOI: 10.1080/15257770.2014.913907

Abstract

β-Ureidopropionase is the third enzyme of the pyrimidine degradation pathway and it catalyzes the conversion of N-carbamyl-β-alanine and N-carbamyl-β-aminoisobutyric acid to β-alanine and β-aminoisobutyric acid, respectively, and ammonia and CO2. To date, only 16 genetically confirmed patients with a complete ß-ureidopropionase deficiency have been reported. Here, we report the clinical, biochemical, and molecular analysis of a newly identified patient with β-ureidopropionase deficiency. Mutation analysis of the UPB1 gene showed that the patient was compound heterozygous for a novel synonymous mutation c.93C>T (p.Gly31Gly) in exon 1 and a previously described missense mutation c.977G>A (p.Arg326Gln) in exon 9. The in silico predicted effect of the synonymous mutation p.Gly31Gly on pre-mRNA splicing was investigated using a minigene approach. Wild-type and the mutated minigene constructs, containing the entire exon 1, intron 1, and exon 2 of UPB1, yielded different splicing products after expression in HEK293 cells. The c.93C>T (p.Gly31Gly) mutation resulted in altered pre-mRNA splicing of the UPB1 minigene construct and a deletion of the last 13 nucleotides of exon 1. This deletion (r.92 104delGCAAGGAACTCAG) results in a frame shift and the generation of a premature stop codon (p.Lys32SerfsX31). Using a minigene approach, we have thus identified the first synonymous mutation in the UPB1 gene, creating a cryptic splice-donor site affecting pre-mRNA splicing.

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