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The clinical differential diagnosis in severely ill neonates, especially in premature infants, is challenging. Next generation sequencing (NGS) diagnostics is a valuable tool, but the turnaround time is often too long to provide a diagnosis in the time needed for clinical guidance in newborn intensive care units (NICU). To minimize turnaround time, we developed an ultra\u2010rapid whole genome sequencing pipeline and tested it in clinical practice. Our pilot case, was a preterm infant presenting with several crises of dehydration, hypoglycaemia and hyponatremia together with nephrocalcinosis and hypertrophic cardiomyopathy. Whole genome sequencing was performed using a paired\u2010end 2x75bp protocol. Sequencing data were exported after 50 sequencing cycles for a first analysis. After run completion, the rapid\u2010sequencing protocol, a second analysis of the 2\u2009x\u200975 paired\u2010end run was performed. Both analyses comprised read\u2010mapping and SNP\u2212\/indel calling on an on\u2010site Edico Genome DRAGEN server, followed by functional annotation and pathogenicity prediction using in\u2010house scripts. After the first analysis within 17\u2009h, the emergency ultra\u2010rapid protocol identified two <jats:italic>novel<\/jats:italic> compound heterozygous variants in the insulin receptor gene (<jats:italic>INSR<\/jats:italic>), pathogenic variants in which cause Donohue Syndrome. The genetic diagnosis could be confirmed by detection of hyperinsulinism and patient care adjusted. Nonetheless, we decided to pursue RNA studies, proving the functional effect of the <jats:italic>novel<\/jats:italic> splice variant and reduced expression levels of <jats:italic>INSR<\/jats:italic> in patients skin fibroblasts.<\/jats:p>","DOI":"10.1002\/ajmg.a.61917","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T17:44:40Z","timestamp":1602611080000},"page":"90-96","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Ultra\u2010rapid emergency genomic diagnosis of Donahue syndrome in a preterm infant within 17\u2009hours"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9868-0184","authenticated-orcid":false,"given":"Daniel","family":"Bamborschke","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC) Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"},{"name":"Department of Pediatrics Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6zkan","family":"\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC) Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"},{"name":"Department of Pediatrics Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Kreutzer","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC) Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"},{"name":"Department of Pediatrics Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Motameny","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Kribs","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"D\u00f6tsch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"Altm\u00fcller","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC) Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"},{"name":"Cologne Center for Genomics (CCG) University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC) Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"},{"name":"Cologne Center for Genomics (CCG) University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebahattin","family":"Cirak","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC) Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"},{"name":"Department of Pediatrics Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2018.02.008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.04.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105262"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.796"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat6177"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-019-03399-4"},{"issue":"23","key":"e_1_2_9_8_1","first-page":"3970","article-title":"Point of care exome sequencing reveals allelic and phenotypic heterogeneity underlying Mendelian disease in Qatar","volume":"28","author":"Fakhro K. 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