{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:10:09Z","timestamp":1791951009320,"version":"4.3.4"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:00:00Z","timestamp":1495756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Vitamin D requires a two-step activation by hydroxylation: The first step is catalyzed by hepatic 25-hydroxylase (CYP2R1, 11p15.2) and the second one is catalyzed by renal 1\u03b1-hydroxylase (CYP27B1, 12q13.1), which produces the active hormonal form of 1,25-(OH)2D. Mutations of CYP2R1 have been associated with vitamin D\u2013dependent rickets type 1B (VDDR1B), a very rare condition that has only been reported to affect 4 families to date. We describe 7 patients from 2 unrelated families who presented with homozygous loss-of-function mutations of CYP2R1. Heterozygous mutations were present in their normal parents. We identified a new c.124_138delinsCGG (p.Gly42_Leu46delinsArg) variation and the previously published c.296T&amp;gt;C (p.Leu99Pro) mutation. Functional in vitro studies confirmed loss-of-function enzymatic activity in both cases. We discuss the difficulties in establishing the correct diagnosis and the specific biochemical pattern, namely, very low 25-OH-D suggestive of classical vitamin D deficiency, in the face of normal\/high concentrations of 1,25-(OH)2D. Siblings exhibited the three stages of rickets based on biochemical and radiographic findings. Interestingly, adult patients were able to maintain normal mineral metabolism without vitamin D supplementation. One index case presented with a partial improvement with 1alfa-hydroxyvitamin D3 or alfacalcidol (1\u03b1-OH-D3) treatment, and we observed a dramatic increase in the 1,25-(OH)2D serum concentration, which indicated the role of accessory 25-hydroxylase enzymes. Lastly, in patients who received calcifediol (25-OH-D3), we documented normal 24-hydroxylase activity (CYP24A1). For the first time, and according to the concept of personalized medicine, we demonstrate dramatic improvements in patients who were given 25-OH-D therapy (clinical symptoms, biochemical data, and bone densitometry). In conclusion, the current study further expands the CYP2R1 mutation spectrum. We note that VDDR1B could be easily mistaken for classical vitamin D deficiency. \u00a9 2017 American Society for Bone and Mineral Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.3181","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T07:48:41Z","timestamp":1495784921000},"page":"1893-1899","source":"Crossref","is-referenced-by-count":74,"title":["Vitamin D\u2013Dependent Rickets Type 1B (25-Hydroxylase Deficiency): A Rare Condition or a Misdiagnosed Condition?"],"prefix":"10.1093","volume":"32","author":[{"given":"Arnaud","family":"Molin","sequence":"first","affiliation":[{"name":"OeReCaUniversit\u00e9 Caen NormandieCaenFrance"},{"name":"BioTARGENUniversit\u00e9 Caen NormandieCaenFrance"},{"name":"Universit\u00e9 Caen NormandieMedical SchoolCaenFrance"},{"name":"CHU de CaenDepartment of Genetics, Molecular Genetics Laboratory and Reference Center for Rare Diseases of Calcium and Phosphorus MetabolismCaenFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Wiedemann","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de LorraineMedical SchoolVandoeuvre-l\u00e8s-NancyFrance"},{"name":"CHU de NancyDepartment of Pediatrics and Reference Center for Rare Hereditary Diseases of MetabolismVandoeuvre-l\u00e8s-NancyFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Demers","sequence":"additional","affiliation":[{"name":"Queen's UniversityDepartment of Biomedical and Molecular SciencesKingstonCanada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Queen's UniversityDepartment of Biomedical and Molecular SciencesKingstonCanada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9my","family":"Do Cao","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de LorraineMedical 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of Calcium and Phosphorus MetabolismCaenFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Richard","sequence":"additional","affiliation":[{"name":"BioTARGENUniversit\u00e9 Caen NormandieCaenFrance"},{"name":"CHU de CaenDepartment of Genetics, Molecular Genetics Laboratory and Reference Center for Rare Diseases of Calcium and Phosphorus MetabolismCaenFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Weryha","sequence":"additional","affiliation":[{"name":"CHU de NancyDepartment of EndocrinologyVandoeuvre-l\u00e8s-NancyFrance"},{"name":"Universit\u00e9 de LorraineMedical SchoolVandoeuvre-l\u00e8s-NancyFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Sorlin","sequence":"additional","affiliation":[{"name":"CHU de NancyDepartment of 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