{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:49:58Z","timestamp":1788306598573,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital defects of the erythrocyte membrane are common in northern Europe and all over the world. The resulting diseases, for example, hereditary spherocytosis (HS), are often underdiagnosed, partly due to their sometimes mild and asymptomatic courses. In addition to a broad clinical spectrum, this is also due to the occasionally complex diagnostics that are not available to every patient. To test whether next-generation sequencing (NGS) could replace time-consuming spherocytosis-specific functional tests, 22 consecutive patients with suspected red cell membranopathy underwent functional blood tests. We were able to identify the causative genetic defect in all patients with suspected HS who underwent genetic testing (n = 17). The sensitivity of the NGS approach, which tests five genes (ANK1 (gene product: ankyrin1), EPB42 (erythrocyte membrane protein band4.2), SLC4A1 (band3), SPTA1 (\u03b1-spectrin), and SPTB (\u03b2-spectrin)), was 100% (95% confidence interval: 81.5\u2013100.0%). The major advantage of genetic testing in the paediatric setting is the small amount of blood required (&lt;200 \u00b5L), and compared to functional assays, sample stability is not an issue. The combination of medical history, basic laboratory parameters, and an NGS panel with five genes is sufficient for diagnosis in most cases. Only in rare cases, a more comprehensive functional screening is required.<\/jats:p>","DOI":"10.3390\/ijms242317021","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T03:58:02Z","timestamp":1701403082000},"page":"17021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hereditary Spherocytosis: Can Next-Generation Sequencing of the Five Most Frequently Affected Genes Replace Time-Consuming Functional Investigations?"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2687-537X","authenticated-orcid":false,"given":"Friederike","family":"H\u00e4user","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7532-8540","authenticated-orcid":false,"given":"Heidi","family":"Rossmann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6237-9840","authenticated-orcid":false,"given":"Anke","family":"Adenaeuer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Marandiuc","sequence":"additional","affiliation":[{"name":"Transfusion Center, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9094-1634","authenticated-orcid":false,"given":"Claudia","family":"Paret","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology & Hemostaseology, Center for Pediatric and Adolescent Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5432-8234","authenticated-orcid":false,"given":"J\u00f6rg","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology & Hemostaseology, Center for Pediatric and Adolescent Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl J.","family":"Lackner","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4538-5154","authenticated-orcid":false,"given":"Bernhard","family":"L\u00e4mmle","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"},{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"},{"name":"Haemostasis Research Unit, University College London, London WC1E6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Beck","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology & Hemostaseology, Center for Pediatric and Adolescent Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/S0140-6736(08)61588-3","article-title":"Hereditary spherocytosis","volume":"372","author":"Perrotta","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/ijlh.12070","article-title":"Hereditary red cell membrane disorders and laboratory diagnostic testing","volume":"35","author":"King","year":"2013","journal-title":"Int. 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