{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:35:39Z","timestamp":1781278539975,"version":"3.54.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n <jats:title><jats:italic>Background:<\/jats:italic><\/jats:title>\n<jats:p>Hypophosphataemic rickets (HR) comprise a clinically and genetically heterogeneous group of conditions, defined by renal-tubular phosphate wasting and consecutive loss of bone mineralisation. X-linked hypophosphataemia (XLH) is the most common form, caused by inactivating dominant mutations in <jats:italic>PHEX<\/jats:italic>, a gene encompassing 22 exons located at Xp22.1. XLH is treatable by anti-Fibroblast Growth Factor 23 antibody, while for other forms of HR such as therapy may not be indicated. Therefore, a genetic differentiation of HR is recommended.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Objective:<\/jats:italic><\/jats:title>\n<jats:p>To develop and validate a next-generation sequencing panel for HR with special focus on <jats:italic>PHEX<\/jats:italic>.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Design and methods:<\/jats:italic><\/jats:title>\n<jats:p>We designed an AmpliSeq gene panel for the IonTorrent PGM next-generation platform for <jats:italic>PHEX<\/jats:italic> and ten other HR-related genes. For validation of <jats:italic>PHEX<\/jats:italic> sequencing 50 DNA-samples from XLH-patients, in whom 42 different mutations in <jats:italic>PHEX<\/jats:italic> and 1 structural variation<jats:italic\/> have been proven before, were blinded, anonymised and investigated with the NGS panel. In addition, we analyzed one known homozygous <jats:italic>DMP1<\/jats:italic> mutation and two samples of HR-patients, where no pathogenic <jats:italic>PHEX<\/jats:italic> mutation had been detected by conventional sequencing.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Results:<\/jats:italic><\/jats:title>\n<jats:p>The panel detected all 42 pathogenic missense\/nonsense\/splice-site\/indel <jats:italic>PHEX<\/jats:italic>-mutations and in one the known homozygous <jats:italic>DMP1<\/jats:italic> mutation. In the remaining two patients, we revealed a somatic mosaicism of a <jats:italic>PHEX<\/jats:italic> mutation in one; as well as two variations in <jats:italic>DMP1<\/jats:italic> and a very rare compound heterozygous variation in <jats:italic>ENPP1<\/jats:italic> in the second patient.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Conclusions:<\/jats:italic><\/jats:title>\n<jats:p>This developed NGS panel is a reliable tool with high sensitivity and specificity for the diagnosis of XLH and related forms of HR.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-20-0275","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T17:22:14Z","timestamp":1597425734000},"page":"497-504","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":12,"title":["Validation of a next-generation sequencing (NGS) panel to improve the diagnosis of X-linked hypophosphataemia (XLH) and other genetic disorders of renal phosphate wasting"],"prefix":"10.1093","volume":"183","author":[{"given":"Susanne","family":"Thiele","sequence":"first","affiliation":[{"name":"1Division of Paediatric Endocrinology and Diabetes, Department of Pediatrics, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Werner","sequence":"additional","affiliation":[{"name":"1Division of Paediatric Endocrinology and Diabetes, Department of Pediatrics, University of L\u00fcbeck, L\u00fcbeck, Germany"},{"name":"2Institute for Molecular Medicine, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Stubbe","sequence":"additional","affiliation":[{"name":"3Labor Dr. Heidrich und Kollegen MVZ GmbH, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Hiort","sequence":"additional","affiliation":[{"name":"1Division of Paediatric Endocrinology and Diabetes, Department of Pediatrics, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hoeppner","sequence":"additional","affiliation":[{"name":"3Labor Dr. Heidrich und Kollegen MVZ GmbH, Hamburg, Germany"},{"name":"4Bioglobe GmbH, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/183\/5\/EJE-20-0275.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/183\/5\/EJE-20-0275.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:14:50Z","timestamp":1676391290000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/183\/5\/497\/6653711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":0,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1530\/eje-20-0275","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11]]}}}