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Clinical, biochemic...
Clinical, biochemical and genetic findings in two siblings with a dihydropyrimidinase deficiency
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van Kuilenburg, André B P (author)
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Meijer, Judith (author)
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- Dobritzsch, Doreen, 1972- (author)
- Karolinska Institutet
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Meinsma, Rutger (author)
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Duran, Marinus (author)
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- Lohkamp, Bernhard (author)
- Karolinska Institutet
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Zoetekouw, Lida (author)
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Abeling, Nico G G M (author)
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van Tinteren, Herman L G (author)
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Bosch, Annet M (author)
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(creator_code:org_t)
- Elsevier BV, 2007
- 2007
- English.
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In: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192 .- 1096-7206. ; 91:2, s. 157-164
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
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- Dihydropyrimidinase (DHP) is the second enzyme of the pyrimidine degradation pathway and it catalyses the ring opening of 5,6-dihydrouracil and 5,6-dihydrothymine to N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid, respectively. To date, only nine individuals have been reported suffering from a complete DHP deficiency. We report two siblings presenting with strongly elevated levels of 5,6-dihydrouracil and 5,6-dihydrothymine in plasma, cerebrospinal fluid and urine. One of the siblings had a severe delay in speech development and white matter abnormalities, whereas the other one was free of symptoms. Analysis of the DHP gene (DPYS) showed that both patients were compound heterozygous for the missense mutation 1078T>C (W360R) in exon 6 and a novel missense mutation 1235G>T (R412M) in exon 7. Heterologous expression of the mutant enzymes in Escherichia coli showed that both missense mutations resulted in a mutant DHP enzyme without residual activity. Analysis of the crystal structure of eukaryotic DHP from the yeast Saccharomyces kluyveri and the slime mold Dictyostelium discoideum suggests that the W360R and R412M mutations lead to structural instability of the enzyme which could potentially impair the assembly of the tetramer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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van Kuilenburg, ...
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Meijer, Judith
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Dobritzsch, Dore ...
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Meinsma, Rutger
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Duran, Marinus
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Lohkamp, Bernhar ...
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show more...
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Zoetekouw, Lida
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Abeling, Nico G ...
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van Tinteren, He ...
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Bosch, Annet M
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Molecular Geneti ...
- By the university
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Uppsala University
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Karolinska Institutet