{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:03:55Z","timestamp":1787321035737,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,2,10]],"date-time":"2017-02-10T00:00:00Z","timestamp":1486684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 577, project A4"],"award-info":[{"award-number":["SFB 577, project A4"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG GRK 2155, project SP6"],"award-info":[{"award-number":["DFG GRK 2155, project SP6"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytometry Part B Clinical"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>\n                    The nuclear morphology of neutrophils depends on different endogenous and exogenous factors, which can lead to hypo\u2010 or hypersegmentation of the normally 2\u20134 segmented nucleus. Hyposegmentation can be due to mutations in the\n                    <jats:italic>LBR\u2010<\/jats:italic>\n                    gene (Pelger\u2010Hu\u00ebt\u2010Anomaly) or can be induced, for example, by colchicine treatment. The range of this phenotypic variation is known as \u201cnorm of reaction,\u201d which can be of major relevance for clinical diagnosis and therapeutic intervention. In this project, we studied the norm of reaction in 26 subjects with 0\u20133 wild type\n                    <jats:italic>LBR<\/jats:italic>\n                    alleles. In addition, the phenotypic variation was analyzed in 3 patients with Familial Mediterranean Fever (FMF), before and after colchicine treatment. We measured the phenotype nuclear segmentation of neutrophils based on two conventional qualitative methods, the \u201crule of threads\u201d and the \u201crule of thirds.\u201d In addition, we tested a morphometric quantitative approach, the \u201ccircularity index.\u201d The circularity index was superior in cases with hyposegmentation; the rule of thirds with respect to hypersegmentation. Approximately 65% of the observed phenotypic variance was explainable by the number of\n                    <jats:italic>LBR<\/jats:italic>\n                    wild type alleles. The gene\u2010dosage effect followed a non\u2010additive, hysteresis\u2010like characteristic with lower and upper plateaus. Colchicine treatment had a clear, although minor phenotypic effect compared to the number of\n                    <jats:italic>LBR<\/jats:italic>\n                    wild type genes or the mutation type. Thus, the nuclear morphology of granulocytes and its norm of reaction can be regarded as an excellent model both for detailing the interplay between endogenous and exogenous factors and for clinical diagnostic purposes. \u00a9 2016 International Clinical Cytometry Society\n                  <\/jats:p>","DOI":"10.1002\/cyto.b.21484","type":"journal-article","created":{"date-parts":[[2016,9,29]],"date-time":"2016-09-29T13:41:33Z","timestamp":1475156493000},"page":"541-549","source":"Crossref","is-referenced-by-count":6,"title":["Image analysis of neutrophil nuclear morphology: Learning about phenotypic range and its reliable analysis from patients with pelger\u2010Hu\u00ebt\u2010anomaly and treated with colchicine"],"prefix":"10.1002","volume":"92","author":[{"given":"Nele","family":"Schnipper","sequence":"first","affiliation":[{"name":"Institute of Medical and Human Genetics, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin D\u201013353 Germany"},{"name":"Institute of Human Genetics, Martin Luther University Halle\u2010Wittenberg Halle D\u201006112 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans H.","family":"Stassen","sequence":"additional","affiliation":[{"name":"Research Group \u201cPsychiatric Genetics and Genetic Epidemiology,\u201d Psychiatric University Hospital Zurich CH\u20108032 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilmann","family":"Kallinich","sequence":"additional","affiliation":[{"name":"Pediatric Pneumology and Immunology and Interdisziplin\u00e4res Sozialp\u00e4diatrisches Zentrum Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin D\u201013353 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Sperling","sequence":"additional","affiliation":[{"name":"Institute of Medical and Human Genetics, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin D\u201013353 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Martin Luther University Halle\u2010Wittenberg Halle D\u201006112 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00412-007-0094-8"},{"key":"e_1_2_6_3_1","volume-title":"Color Atlas of Hematolog\u2010Practical Microscopic and Clinical Diagnosis","author":"Theml H","year":"2004"},{"key":"e_1_2_6_4_1","volume-title":"Blood Cell Morphology: Grading Guide","author":"Gulati G.","year":"2009"},{"key":"e_1_2_6_5_1","volume-title":"Hematology Basic Principles and Practice","author":"Curnutte JT","year":"2000"},{"key":"e_1_2_6_6_1","first-page":"96","article-title":"Effect of colchicine on the white blood picture of Pelger and non\u2010Pelger 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