{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:09:36Z","timestamp":1774645776754,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[1999,5,1]],"date-time":"1999-05-01T00:00:00Z","timestamp":925516800000},"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":[[1999,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pseudovitamin D\u2013defiency rickets (PDDR) is an autosomal recessive disorder characterized by hypocalcemia, rickets (which are resistant to treatment with vitamin D), and low or undetectable serum levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). The symptoms are corrected with 1,25(OH)2D treatment, and the disease is now believed to result from a defect in the cytochrome P450 component (P450c1; CYP27B1) of the renal 25-hydroxyvitamin D-1\u03b1-hydroxylase (1-OHase). We have studied genomic DNA from three families with PDDR and have identified the same homozygous mutation in the P450c1 gene in two of the index cases, causing a frameshift in exon 8, resulting in a premature stop codon in the heme-binding domain. The two cases in the third kindred were compound heterozygotes with missense mutations in exons 6 and 9. We have also identified a C\/T polymorphism in intron 6 of the P450c1 genomic DNA. Interferon \u03b3\u2013inducible 1-OHase activity in blood-derived macrophages was shown by 1,25(OH)2D synthesis in all control cells tested (37\u2013184 fmol\/h\/106 cells) and those from the PDDR family parents (34\u2013116 fmol\/h\/106 cells) but was totally absent from the patients' cells, indicating a defect in their macrophage 1-OHase, similar to the presumed renal defect. The assumption of similarity between the renal and macrophage P450c1 was supported by our ability to clone a 514 bp sequence, including the heme-binding region of the macrophage P450c1 cDNA from controls, which was identical to that published for both the renal and keratinocyte P450c1 cDNAs.<\/jats:p>","DOI":"10.1359\/jbmr.1999.14.5.730","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T20:14:41Z","timestamp":1146082481000},"page":"730-739","source":"Crossref","is-referenced-by-count":78,"title":["Novel Mutations in the 1\u03b1-Hydroxylase (P450c1) Gene in Three Families with Pseudovitamin D\u2013Deficiency Rickets Resulting in Loss of Functional Enzyme Activity in Blood-Derived Macrophages"],"prefix":"10.1093","volume":"14","author":[{"given":"S. J.","family":"Smith","sequence":"first","affiliation":[{"name":"These two authors made an equal contribution to the project., St. Mary's Hospital, Manchester, United Kingdom"},{"name":"University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. K.","family":"Rucka","sequence":"additional","affiliation":[{"name":"University Department of Medical Genetics and Regional Genetics Service, St. Mary's Hospital, Manchester, United Kingdom"},{"name":"These two authors made an equal contribution to the project., St. Mary's Hospital, Manchester, United Kingdom"},{"name":"University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. L.","family":"Berry","sequence":"additional","affiliation":[{"name":"University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Davies","sequence":"additional","affiliation":[{"name":"University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Mylchreest","sequence":"additional","affiliation":[{"name":"University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. R.","family":"Paterson","sequence":"additional","affiliation":[{"name":"University Department of Medicine, Ninewells Hospital and Medical School, Dundee, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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