{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:17:03Z","timestamp":1788952623199,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,2,14]],"date-time":"2014-02-14T00:00:00Z","timestamp":1392336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u03b2\u2010ureidopropionase (\u03b2UP) deficiency is an autosomal recessive disease characterized by N\u2010carbamyl\u2010\u03b2\u2010amino aciduria. To date, only 16 genetically confirmed patients with \u03b2UP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese \u03b2UP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant \u03b2UP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (\u2264 1.3 %). Conversely, \u03b2UP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non\u2010coding region of the<jats:italic>UPB1<\/jats:italic>gene. Analysis of a human \u03b2UP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that \u03b2UP deficiency is not as rare as generally considered and screening for \u03b2UP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities.<\/jats:p>","DOI":"10.1007\/s10545-014-9682-y","type":"journal-article","created":{"date-parts":[[2014,2,13]],"date-time":"2014-02-13T14:58:19Z","timestamp":1392303499000},"page":"801-812","source":"Crossref","is-referenced-by-count":27,"title":["Clinical, biochemical and molecular analysis of 13 Japanese patients with \u03b2\u2010ureidopropionase deficiency demonstrates high prevalence of the c.977G &gt; A (p.R326Q) mutation"],"prefix":"10.1002","volume":"37","author":[{"given":"Yoko","family":"Nakajima","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases Academic Medical Center Amsterdam 1105 AZ Netherlands"},{"name":"Department of Pediatrics and Neonatology Nagoya City University Graduate School of Medical Sciences Nagoya 467\u20108601 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Meijer","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases Academic Medical Center Amsterdam 1105 AZ Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doreen","family":"Dobritzsch","sequence":"additional","affiliation":[{"name":"Department of Chemistry Uppsala University, BMC Uppsala 75123 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neonatology Nagoya City University Graduate School of Medical Sciences Nagoya 467\u20108601 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutger","family":"Meinsma","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases Academic Medical Center Amsterdam 1105 AZ Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico G. 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