{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:36:35Z","timestamp":1789580195401,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,8,13]],"date-time":"2014-08-13T00:00:00Z","timestamp":1407888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Folkh\u00e4lsan Research Foundation"},{"name":"Sigrid Juselius Foundation"},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>X\u2010linked hypophosphatemia (XLH) is caused by mutations in <jats:italic>PHEX<\/jats:italic>. Several other genetic forms of hypophosphatemia have also been described. These disorders share variable clinical presentation ranging from mild hypophosphatemia to severe lower extremity bowing. We report on a 43\u2010year\u2010old woman with short stature, painful leg deformities, and poor dentation. Her biochemical profile showed hypophosphatemia with renal phosphate wasting. Due to unusually severe clinical presentation and absence of mutations in Sanger sequencing of the <jats:italic>PHEX<\/jats:italic> gene, quantitative multiplex ligation\u2010dependent probe amplification was performed. A large deletion within the <jats:italic>PHEX<\/jats:italic> gene encompassing exons 8 to 11 was identified. We generated a specific junction fragment using long\u2010range PCR and sequenced the junction fragment to determine the exact deletion breakpoints. We found a heterozygous novel complex re\u2010arrangement involving gross deletions, insertions, and inversion of <jats:italic>PHEX<\/jats:italic> (hg19:g.22,115,003_22,141,395del;g:22,145,536_22,150,789delinsCins22,114,640_22,114,698invinsA). Thus, the complex re\u2010arrangement including a deletion of coding exons 8 to 11 of the <jats:italic>PHEX<\/jats:italic> can be regarded as the cause of XLH in the patient reported here. Phosphate and active vitamin D treatment was initiated with subsequent relief in bone pain and physical improvement. This report expands the spectrum of clinical severity underlying genetic defects in XLH and highlights the importance of conventional medical therapy even at adult age. Furthermore, our findings underscore the importance of search for gene deletions in patients with suspected XLH. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36721","type":"journal-article","created":{"date-parts":[[2014,8,13]],"date-time":"2014-08-13T22:03:58Z","timestamp":1407967438000},"page":"2931-2937","source":"Crossref","is-referenced-by-count":7,"title":["Unusually severe hypophosphatemic rickets caused by a novel and complex re\u2010arrangement of the <i>PHEX<\/i> gene"],"prefix":"10.1002","volume":"164","author":[{"given":"Tuula","family":"Pekkarinen","sequence":"first","affiliation":[{"name":"Division of Endocrinology Department of Medicine Helsinki University Central Hospital Vantaa Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Lorenz\u2010Depiereux","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Helmholtz Center Munich Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Lohman","sequence":"additional","affiliation":[{"name":"HUS Medical Imaging Center Helsinki University Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology and Metabolic Bone Diseases Children's Hospital Helsinki University Central Hospital and University of Helsinki Helsinki Finland"},{"name":"Folkh\u00e4lsan Institute of Genetics Helsinki Finland"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet and Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,13]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"130","article-title":"The HYP Consortium","volume":"11","author":"A gene (PEX) with 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