{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:01:26Z","timestamp":1791478886201,"version":"4.3.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Hereditary alpha tryptasemia (H\u03b1T) has significant prevalence and potential morbidity in the general population. However, it remains largely undiagnosed in routine clinical diagnostics due to low availability of efficient assessment methods. To address this issue, we developed a reliable and efficient single-well multiplex digital droplet PCR assay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The assay was based on the reconstruction of the TPSAB1 gene through quantification of the ratio of \u03b1- and \u03b2-tryptase copy number variants (CNV) in a single-well measurement. We performed analytical validation by determining CNV measurement clustering around the expected copy numbers in 281 cases and determined the diagnostic accuracy of basal serum tryptase (BST) to predict H\u03b1T and H\u03b1T subtypes in 141 symptomatic patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The assay determined \u03b1- and \u03b2-tryptase CNVs with an overall accuracy, expressed as a 99% prediction interval, of 0.03 \u00b1 0.27 copy numbers. The optimal BST cutoff level to predict H\u03b1T in symptomatic patients, who had no other explanation for relatively high tryptase levels (i.e., no diagnosis of systemic mastocytosis, myeloid neoplasm, or end-stage renal failure), was 9.2\u2005ng\/mL (sensitivity: 98.1%; specificity: 96.6%). H\u03b1T showed a linear gene\u2013dose effect, with an average gene\u2013dose increase of 7.5\u2005ng\/mL per extra \u03b1-tryptase gene.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our single-well multiplex digital droplet PCR assay accurately determined H\u03b1T and could be implemented as a state-of-the-art routine diagnostic test. The assay demonstrated a strong correlation with BST and the optimal threshold for identifying H\u03b1T in symptomatic patients with unexplained high tryptase concentrations was at a BST level of 9.2\u2005ng\/mL.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvad206","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T14:26:16Z","timestamp":1702304776000},"page":"425-433","source":"Crossref","is-referenced-by-count":7,"title":["Hereditary Alpha Tryptasemia: Validation of a Single-Well Multiplex Digital Droplet PCR Assay in a Cohort of Symptomatic Patients"],"prefix":"10.1093","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-8987","authenticated-orcid":false,"given":"Abdulrazzaq","family":"Alheraky","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albertus T J","family":"Wierenga","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"},{"name":"Department of Hematology, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan","family":"Simpelaar","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy B","family":"Hesp","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidor","family":"Minovic","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niusha","family":"Bagheri","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Roozendaal","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lambert F R","family":"Span","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanneke N G","family":"Oude Elberink","sequence":"additional","affiliation":[{"name":"Department of Allergology, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido P","family":"Kema","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 B","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University 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