{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:43:23Z","timestamp":1787244203813,"version":"build-2736575974"},"reference-count":0,"publisher":"Bioscientifica","issue":"6","content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,6]]},"abstract":"\n Introduction<\/jats:title>\n \n Inactivating mutations in\n CYP24A1<\/jats:italic>\n , encoding vitamin D-24-hydroxylase, can lead to an accumulation of active vitamin D metabolites and consequent hypercalcaemia. Patient (infantile and adult) presentation is varied and includes mild-severe hypercalcaemia, hypercalciuria, nephrocalcinosis and nephrolithiasis. This study aimed to characterize the clinical and biochemical phenotypes of a family with two\n CYP24A1<\/jats:italic>\n missense variants.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The proband and seven family members underwent detailed clinical and biochemical evaluation. Laboratory measurements included serum calcium, intact parathyroid hormone (iPTH), vitamin D metabolites and urine calcium and creatinine.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The proband presented during the second trimester of a planned pregnancy with flu-like symptoms. Laboratory tests showed elevated adjusted calcium of 3.27 (upper reference limit (URL: 2.30) mmol\/L), suppressed iPTH (<6 ng\/L), elevated 25(OH)D (264 (URL: 55) nmol\/L) and elevated 1,25(OH)D (293 (URL: <280) pmol\/L). Ionized calcium was 1.55 (URL: 1.28) mmol\/L. Sanger sequencing revealed two heterozygous missense variants in the\n CYP24A1<\/jats:italic>\n : p.(Arg439Cys), R439C and p.(Trp275Arg), W275R. The proband\u2019s brother and sister had the same genotype. The brother had intermittent hypercalcaemia and hypervitaminosis D. Only the sister had a history of nephrolithiasis. The proband\u2019s daughter and two nephews were heterozygous for the R439C variant. The proband and her brother frequently had elevated 25(OH)D:24,25(OH)\n 2<\/jats:sub>\n D ratios (>50) during follow-up.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n W275R is a new pathogenic CYP24A1 mutation in compound heterozygotic form with R439C in this family.<\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/ec-20-0150","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T14:59:36Z","timestamp":1588777176000},"page":"530-541","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":18,"title":["Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes"],"prefix":"10.1530","volume":"9","author":[{"given":"Tom\u00e1s P","family":"Griffin","sequence":"first","affiliation":[{"name":"1Centre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, Ireland"},{"name":"2Regenerative Medicine Institute at C\u00daRAM SFI Research Centre, School of Medicine, National University of Ireland Galway (NUIG), Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M","family":"Joyce","sequence":"additional","affiliation":[{"name":"3Department of Clinical Biochemistry, Cork University Hospital, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaya","family":"Alkanderi","sequence":"additional","affiliation":[{"name":"4Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam M","family":"Blake","sequence":"additional","affiliation":[{"name":"5Department of Clinical Biochemistry, SUHCG, GUH, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek T","family":"O\u2019Keeffe","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"Bogdanet","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Nahidul","family":"Islam","sequence":"additional","affiliation":[{"name":"2Regenerative Medicine Institute at C\u00daRAM SFI Research Centre, School of Medicine, National University of Ireland Galway (NUIG), Galway, Ireland"},{"name":"5Department of Clinical Biochemistry, SUHCG, GUH, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C","family":"Dennedy","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, Ireland"},{"name":"6Lambe Institute for Translational Research, School of Medicine, NUIG, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E","family":"Gillan","sequence":"additional","affiliation":[{"name":"7Department of Histopathology, SUHCG, GUH, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"Morrison","sequence":"additional","affiliation":[{"name":"8Department of Obstetrics and Gynaecology, SUHCG, GUH, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, Ireland"},{"name":"2Regenerative Medicine Institute at C\u00daRAM SFI Research Centre, School of Medicine, National University of Ireland Galway (NUIG), Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A","family":"Sayer","sequence":"additional","affiliation":[{"name":"4Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK"},{"name":"9Newcastle upon Tyne NHS Hospitals Foundation Trust, Newcastle upon Tyne, UK"},{"name":"10NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"Bell","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M","family":"O\u2019Shea","sequence":"additional","affiliation":[{"name":"5Department of Clinical Biochemistry, SUHCG, GUH, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/9\/6\/EC-20-0150.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/9\/6\/EC-20-0150.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:44:00Z","timestamp":1784555040000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/9\/6\/530-541\/686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6]]},"references-count":0,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/ec-20-0150","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6]]}}}