{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:56:39Z","timestamp":1791143799313,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,8,14]],"date-time":"2012-08-14T00:00:00Z","timestamp":1344902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Vitamin <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\u2010dependent rickets type 1<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">VDDR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> OMIM<\/jats:styled-content> 264700) is a rare autosomal recessive disorder and is caused by mutations in the <jats:styled-content style=\"fixed-case\"><jats:italic>CYP27B1<\/jats:italic><\/jats:styled-content> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We aim to investigate <jats:styled-content style=\"fixed-case\"><jats:italic>CYP27B1<\/jats:italic><\/jats:styled-content> mutation in seven patients from four separate families and characterize the genotype\u2013phenotype correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The entire coding region of the <jats:styled-content style=\"fixed-case\"><jats:italic>CYP27B1<\/jats:italic><\/jats:styled-content> gene was sequenced, and genotype\u2013phenotype correlation among patients was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequencing analysis identified biallelic <jats:styled-content style=\"fixed-case\"><jats:italic>CYP27B1<\/jats:italic><\/jats:styled-content> mutations in all patients and monoallelic mutations in their parents. One patient from the first family was compound heterozygous for c.1166G&gt;<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> (p.<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>rg389<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>is) and a novel nonsense mutation c.1079 <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>&gt;<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> (p.<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>er360*). Two patients from the second family were homozygous for a novel splice donor site mutation in intron 1 (c.195\u00a0+\u00a02 <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>&gt;<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>), causing partial retention of the intron and a shift in the reading frame. Both novel mutations lead to the complete loss of vitamin <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>1\u03b1\u2010hydroxylase activity. Four patients from families 3 and 4 were homozygous for a previously reported duplication mutation in exon 8 (1319\u20131325dup<jats:styled-content style=\"fixed-case\">CCCACCC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> P<\/jats:styled-content>he443<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>rofs*24). Interestingly, one patient who was presented with severe hypocalcaemia and seizures at 4\u00a0months of age as a result of <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>he443<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>rofs*24 has improved spontaneously since 11\u00a0years of age and does not need regular treatment. Her laboratory tests showed normal serum calcium and 1,25(<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>)<jats:sub>2<\/jats:sub><jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> after refusing to take medication for 12\u00a0months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>There is a good genotype\u2013phenotype correlation in <jats:styled-content style=\"fixed-case\">VDDR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>. However, some patients may recover from the loss of <jats:styled-content style=\"fixed-case\"><jats:italic>CYP27B1<\/jats:italic><\/jats:styled-content> function, probably due to 1\u03b1\u2010hydroxylase activity exerted by a non\u2010<jats:styled-content style=\"fixed-case\"><jats:italic>CYP27B1<\/jats:italic><\/jats:styled-content> enzyme.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2265.2012.04394.x","type":"journal-article","created":{"date-parts":[[2012,3,24]],"date-time":"2012-03-24T12:42:27Z","timestamp":1332592947000},"page":"363-369","source":"Crossref","is-referenced-by-count":46,"title":["Clinical and genetic analysis of patients with vitamin <scp>D<\/scp>\u2010dependent rickets type 1<scp>A<\/scp>"],"prefix":"10.1111","volume":"77","author":[{"given":"Erdem","family":"Durmaz","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology Akdeniz University School of Medicine Antalya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjing","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital &amp; Research Centre Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roua A.","family":"Al\u2010Rijjal","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital &amp; Research Centre Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130ffet","family":"Bircan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Akdeniz University School of Medicine Antalya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sema","family":"Ak\u00e7urin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Akdeniz University School of Medicine Antalya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital &amp; Research Centre Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital &amp; 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