{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:56:30Z","timestamp":1789559790203,"version":"build-2803163510"},"reference-count":23,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T00:00:00Z","timestamp":1622851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Nutrition Obesity Research Center at the University of Washington","award":["P30 DK035816"],"award-info":[{"award-number":["P30 DK035816"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Circulating plasma vitamin D metabolites are highly bound to vitamin D-binding protein (DBP), also known as group-specific component or Gc-globulin. DBP, encoded by the GC gene, is a member of the albumin family of globular serum transport proteins. We previously described a homozygous GC gene deletion in a patient with apparent severe vitamin D deficiency, fragility fractures, and ankylosing spondylitis. Here, we report an unrelated patient free of fractures or rheumatologic disease, but with very low 25-hydroxyvitamin D and 1,25-hydroxyvitamin D, as well as undetectable DBP measured by liquid chromatography\u2013tandem mass spectrometry. A whole gene deletion was excluded by microarray, and Sanger sequencing of GC revealed a homozygous pathogenic variant affecting a canonical splice site (c0.702-1G\u2005&amp;gt;\u2005A). These findings indicate that loss of function variants in GC that eliminate DBP, and severely reduced total circulating vitamin D levels, do not necessarily result in significant metabolic bone disease. Together with our previous report, these cases support the free-hormone hypothesis, and suggest free vitamin D metabolites may serve as preferable indicators of bone and mineral metabolism, particularly when clinical suspicion of DBP deficiency is high.<\/jats:p>","DOI":"10.1210\/jendso\/bvab104","type":"journal-article","created":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T19:08:44Z","timestamp":1622920124000},"source":"Crossref","is-referenced-by-count":16,"title":["Very Low Vitamin D in a Patient With a Novel Pathogenic Variant in the <i>GC<\/i> Gene That Encodes Vitamin D-Binding Protein"],"prefix":"10.1210","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8310-251X","authenticated-orcid":false,"given":"Ronadip R","family":"Banerjee","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA"},{"name":"Endocrinology Section, Medical Service, Veterans Affairs Medical Center, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Spence","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, Alberta Precision Laboratories, Calgary, Alberta T3B 6A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J","family":"Frank","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA"},{"name":"Endocrinology Section, Medical Service, Veterans Affairs Medical Center, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Pandian","sequence":"additional","affiliation":[{"name":"Pan Laboratories, Irvine, CA 92618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew N","family":"Hoofnagle","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine and Pathology, Kidney Research Institute, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9638-9126","authenticated-orcid":false,"given":"Bob","family":"Argiropoulos","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, Alberta Precision Laboratories, Calgary, Alberta T3B 6A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien L","family":"Marcadier","sequence":"additional","affiliation":[{"name":"The University of Calgary, and the Division of Medical Genetics, Alberta Children\u2019s Hospitals, Calgary, Alberta T3B 6A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,6,5]]},"reference":[{"issue":"3","key":"2021110514394448500_CIT0001","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N Engl J Med."},{"key":"2021110514394448500_CIT0002","doi-asserted-by":"crossref","first-page":"910","DOI":"10.3389\/fendo.2019.00910","article-title":"Vitamin D binding protein: a historic overview","volume":"10","author":"Bouillon","year":"2019","journal-title":"Front Endocrinol."},{"issue":"3","key":"2021110514394448500_CIT0003","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/0167-4781(93)90005-X","article-title":"Sequence and organization of the human vitamin D-binding protein gene","volume":"1216","author":"Braun","year":"1993","journal-title":"Biochim Biophys 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