{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:41:14Z","timestamp":1792788074127,"version":"4.5.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T00:00:00Z","timestamp":1577664000000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority","award":["XTYB201808"],"award-info":[{"award-number":["XTYB201808"]}]},{"name":"The Public Health Project for Residents in Beijing","award":["Z151100003915103"],"award-info":[{"award-number":["Z151100003915103"]}]},{"name":"The National Key Research and Development Program of China","award":["2016YFC0901505"],"award-info":[{"award-number":["2016YFC0901505"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antley-Bixler syndrome (ABS) caused by P450 oxidoreductase deficiency (PORD) is a congenital adrenal hyperplasia with skeletal malformations and disordered sex development in both sexes. There have been no reports of ABS caused by PORD in Chinese children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We described the clinical and genetic characteristics of eight Chinese children with ABS caused by PORD and compared them with those of subjects in previous studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight patients, aged 6\u2009months\u201317.8\u2009years, showed strikingly similar craniofacial malformations. We first described four unreported features: lower eyelid fat pads (4\/8), prominent lower eyelid-zygoma transverse line (4\/8), underdeveloped or absent antihelix (5\/8) and single earlobe crease (5\/8). Five 46, XY patients presented various degrees of undervirilization, while three 46, XX cases showed masculinization. Basal endocrine measurements revealed the following consistent results: normal cortisol; elevated adrenocorticotropic hormone, progesterone, pregnenolone, 17-hydroxypropgesterone, and corticosterone; and decreased or normal testosterone\/oestradiol. We identified three previously reported variants and four novel variants (c.51719_51710delGGCCCCTGTGinsC, p.D210G, p.Y248X and p.R554X) of\n                      <jats:italic>POR<\/jats:italic>\n                      . The most prevalent variant was p.R457H (8\/16). The hydrocortisone dosages of patients differed because of variable degrees of adrenal insufficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We described novel phenotypes and genotypes of ABS caused by PORD. The variant p.R457H was the most prevalent in this cohort. All subjects had combined characteristics of 17-hydroxylase and 21-hydroxylase deficiency. Steroid replacement therapy for patients with PORD requires individually tailored dosing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-019-1283-2","type":"journal-article","created":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T13:02:22Z","timestamp":1577710942000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Novel phenotypes and genotypes in Antley-Bixler syndrome caused by cytochrome P450 oxidoreductase deficiency: based on the first cohort of Chinese children"],"prefix":"10.1186","volume":"14","author":[{"given":"Lijun","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoya","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanning","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfen","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiu","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,30]]},"reference":[{"issue":"5","key":"1283_CR1","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1159\/000114857","volume":"69","author":"RR Scott","year":"2008","unstructured":"Scott RR, Miller WL. Genetic and clinical features of p450 oxidoreductase deficiency. Horm Res. 2008;69(5):266\u201375.","journal-title":"Horm Res"},{"issue":"2","key":"1283_CR2","first-page":"397","volume":"11","author":"R Antley","year":"1975","unstructured":"Antley R, Bixler D. Trapezoidocephaly, midfacial hypoplasia and cartilage abnormalities with multiple synostoses and skeletal fractures. Birth Defects Orig Artic Ser. 1975;11(2):397\u2013401.","journal-title":"Birth Defects Orig Artic Ser"},{"issue":"3","key":"1283_CR3","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/ng1300","volume":"36","author":"CE Fluck","year":"2004","unstructured":"Fluck CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, et al. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet. 2004;36(3):228\u201330.","journal-title":"Nat Genet"},{"issue":"6","key":"1283_CR4","doi-asserted-by":"publisher","first-page":"2318","DOI":"10.1210\/jc.2006-2345","volume":"92","author":"RR Scott","year":"2007","unstructured":"Scott RR, Gomes LG, Huang N, Van Vliet G, Miller WL. Apparent manifesting heterozygosity in P450 oxidoreductase deficiency and its effect on coexisting 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2007;92(6):2318\u201322.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"1283_CR5","doi-asserted-by":"publisher","first-page":"2732","DOI":"10.1210\/en.2009-0043","volume":"150","author":"A Aguilar","year":"2009","unstructured":"Aguilar A, Wu S, De Luca F. P450 oxidoreductase expressed in rat chondrocytes modulates chondrogenesis via cholesterol- and Indian hedgehog-dependent mechanisms. Endocrinology. 2009;150(6):2732\u20139.","journal-title":"Endocrinology"},{"issue":"6","key":"1283_CR6","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1530\/EJE-10-0764","volume":"163","author":"D Tomalik-Scharte","year":"2010","unstructured":"Tomalik-Scharte D, Maiter D, Kirchheiner J, Ivison HE, Fuhr U, Arlt W. Impaired hepatic drug and steroid metabolism in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. Eur J Endocrinol. 2010;163(6):919\u201324.","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"1283_CR7","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s11154-007-9056-y","volume":"8","author":"W Arlt","year":"2007","unstructured":"Arlt W. P450 oxidoreductase deficiency and Antley-Bixler syndrome. Rev Endocr Metab Disord. 2007;8(4):301\u20137.","journal-title":"Rev Endocr Metab Disord"},{"issue":"1","key":"1283_CR8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13048-017-0312-9","volume":"10","author":"Y Bai","year":"2017","unstructured":"Bai Y, Li J, Wang X. Cytochrome P450 oxidoreductase deficiency caused by R457H mutation in POR gene in Chinese: case report and literature review. J Ovarian Res. 2017;10(1):16.","journal-title":"J Ovarian Res"},{"issue":"5","key":"1283_CR9","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324.","journal-title":"Genet Med"},{"key":"1283_CR10","volume-title":"GeneReviews((R))","author":"J Idkowiak","year":"1993","unstructured":"Idkowiak J, Cragun D, Hopkin RJ, Arlt W. Cytochrome P450 Oxidoreductase deficiency. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al., editors. GeneReviews((R)). Seattle (WA): University of Washington; 1993. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved."},{"issue":"7","key":"1283_CR11","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1016\/j.ijporl.2007.02.016","volume":"71","author":"AA McCall","year":"2007","unstructured":"McCall AA, Kirsch CF, Ishiyama G, Ishiyama A. Otologic findings in Antley-Bixler syndrome: a clinical and radiologic case report. Int J Pediatr Otorhinolaryngol. 2007;71(7):1139\u201343.","journal-title":"Int J Pediatr Otorhinolaryngol"},{"issue":"9427","key":"1283_CR12","doi-asserted-by":"publisher","first-page":"2128","DOI":"10.1016\/S0140-6736(04)16503-3","volume":"363","author":"W Arlt","year":"2004","unstructured":"Arlt W, Walker EA, Draper N, Ivison HE, Ride JP, Hammer F, et al. Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study. Lancet (London, England). 2004;363(9427):2128\u201335.","journal-title":"Lancet (London, England)"},{"key":"1283_CR13","volume-title":"Endotext","author":"S Domenice","year":"2000","unstructured":"Domenice S, Arnhold IJP, Costa EMF, Mendonca BB. 46,XY disorders of sexual development. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, et al., editors. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000."},{"issue":"3","key":"1283_CR14","doi-asserted-by":"publisher","first-page":"E453","DOI":"10.1210\/jc.2010-1607","volume":"96","author":"J Idkowiak","year":"2011","unstructured":"Idkowiak J, O'Riordan S, Reisch N, Malunowicz EM, Collins F, Kerstens MN, et al. Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. J Clin Endocrinol Metab. 2011;96(3):E453\u201362.","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"1283_CR15","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1210\/jc.2008-2816","volume":"94","author":"M Fukami","year":"2009","unstructured":"Fukami M, Nishimura G, Homma K, Nagai T, Hanaki K, Uematsu A, et al. Cytochrome P450 oxidoreductase deficiency: identification and characterization of biallelic mutations and genotype-phenotype correlations in 35 Japanese patients. J Clin Endocrinol Metab. 2009;94(5):1723\u201331.","journal-title":"J Clin Endocrinol Metab"},{"issue":"Pt A","key":"1283_CR16","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jsbmb.2016.04.003","volume":"165","author":"FZ Burkhard","year":"2017","unstructured":"Burkhard FZ, Parween S, Udhane SS, Fluck CE, Pandey AV. P450 oxidoreductase deficiency: analysis of mutations and polymorphisms. J Steroid Biochem Mol Biol. 2017;165(Pt A):38\u201350.","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"2","key":"1283_CR17","doi-asserted-by":"publisher","first-page":"E257","DOI":"10.1210\/jc.2011-0640","volume":"97","author":"N Krone","year":"2012","unstructured":"Krone N, Reisch N, Idkowiak J, Dhir V, Ivison HE, Hughes BA, et al. Genotype-phenotype analysis in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. J Clin Endocrinol Metab. 2012;97(2):E257\u201367.","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"1283_CR18","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1086\/429417","volume":"76","author":"N Huang","year":"2005","unstructured":"Huang N, Pandey AV, Agrawal V, Reardon W, Lapunzina PD, Mowat D, et al. Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. Am J Hum Genet. 2005;76(5):729\u201349.","journal-title":"Am J Hum Genet"},{"issue":"10","key":"1283_CR19","doi-asserted-by":"publisher","first-page":"2579","DOI":"10.1210\/me.2007-0245","volume":"21","author":"AV Pandey","year":"2007","unstructured":"Pandey AV, Kempna P, Hofer G, Mullis PE, Fluck CE. Modulation of human CYP19A1 activity by mutant NADPH P450 oxidoreductase. Mol Endocrinol (Baltimore, Md). 2007;21(10):2579\u201395.","journal-title":"Mol Endocrinol (Baltimore, Md)"},{"issue":"12","key":"1283_CR20","doi-asserted-by":"publisher","first-page":"4992","DOI":"10.1210\/jc.2009-1460","volume":"94","author":"T Sahakitrungruang","year":"2009","unstructured":"Sahakitrungruang T, Huang N, Tee MK, Agrawal V, Russell WE, Crock P, et al. Clinical, genetic, and enzymatic characterization of P450 oxidoreductase deficiency in four patients. J Clin Endocrinol Metab. 2009;94(12):4992\u20135000.","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-019-1283-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13023-019-1283-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-019-1283-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T19:21:13Z","timestamp":1609183273000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-019-1283-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1283"],"URL":"https:\/\/doi.org\/10.1186\/s13023-019-1283-2","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"4 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The research protocol was approved by the ethics committee of Beijing Children\u2019s Hospital, Capital Medical University (ID: 2012\u201328), and written informed consent was received from all patients or legal guardians.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent was obtained from all patients for publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"299"}}