{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T09:01:55Z","timestamp":1792227715079,"version":"4.4.0"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,7,16]],"date-time":"2018-07-16T00:00:00Z","timestamp":1531699200000},"content-version":"vor","delay-in-days":45,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Investigation"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Importance<\/jats:title><jats:p>Cytochrome P450 oxidoreductase deficiency (<jats:styled-content style=\"fixed-case\">PORD<\/jats:styled-content>) is a rare disease exhibiting a variety of clinical manifestations. This condition specifically leads to disordered steroidogenesis, which can affect the development of the reproductive system, skeleton, and other parts of the body. The severe form of <jats:styled-content style=\"fixed-case\">PORD<\/jats:styled-content> is difficult to differentiate with Antley\u2010Bixler syndrome (<jats:styled-content style=\"fixed-case\">ABS<\/jats:styled-content>). The genetic characters and clinical evaluation of <jats:styled-content style=\"fixed-case\">PORD<\/jats:styled-content> are still unclear in China.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To perform an exome analysis and identify the pathogenic cause in order to assist clinicians to obtain a proper evaluation on the genetic condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The proband underwent detailed physical evaluations. <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> of the proband and his parents was isolated and whole\u2010exome sequencing (<jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content>) was performed. Variants were analyzed and evaluation according to the <jats:styled-content style=\"fixed-case\">ACMG<\/jats:styled-content> guideline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 1\u2010year\u2010old Chinese boy with midface hypoplasia, choanal stenosis, multiple joint contractures, micropenis and right cryptorchidism was misdiagnosed with Crouzon syndrome. By trio\u2010whole\u2010exome sequencing, we identified an unreported compound heterozygous mutation (c.667C&gt;T, p.R223* and c.1370G&gt;A, p.R457H) in <jats:italic><jats:styled-content style=\"fixed-case\">POR<\/jats:styled-content><\/jats:italic> in the proband. This mutation was inherited from healthy heterozygous parents, supporting the diagnosis of <jats:styled-content style=\"fixed-case\">PORD<\/jats:styled-content>, which was further confirmed by biochemical characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We have identified a pathogenic variant with an unreported compound heterozygous <jats:italic><jats:styled-content style=\"fixed-case\">POR<\/jats:styled-content><\/jats:italic> mutation, which expands the clinical and genetic spectra of <jats:styled-content style=\"fixed-case\">PORD<\/jats:styled-content> and emphasizes the usefulness of <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> for genetic diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ped4.12035","type":"journal-article","created":{"date-parts":[[2018,7,16]],"date-time":"2018-07-16T08:09:31Z","timestamp":1531728571000},"page":"90-95","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Compound heterozygous variants in <i><scp>POR<\/scp><\/i> gene identified by whole\u2010exome sequencing in a Chinese pedigree with cytochrome P450 oxidoreductase deficiency"],"prefix":"10.1002","volume":"2","author":[{"given":"Chanjuan","family":"Hao","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory for Genetics of Birth Defects MOE Key Laboratory of Major Diseases in Children Center for Medical Genetics Beijing Pediatric Research Institute Capital Medical University National Center for Children's Health Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Guo","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Genetics of Birth Defects MOE Key Laboratory of Major Diseases in Children Center for Medical Genetics Beijing Pediatric Research Institute Capital Medical University National Center for Children's Health Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolan","family":"Guo","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Genetics of Birth Defects MOE Key Laboratory of Major Diseases in Children Center for Medical Genetics Beijing Pediatric Research Institute Capital Medical University National Center for Children's Health Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Qi","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Genetics of Birth Defects MOE Key Laboratory of Major Diseases in Children Center for Medical Genetics Beijing Pediatric Research Institute Capital Medical University National Center for Children's Health Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Genetics of Birth Defects MOE Key Laboratory of Major Diseases in Children Center for Medical Genetics Beijing Pediatric Research Institute Capital Medical University National Center for Children's Health Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ni","sequence":"additional","affiliation":[{"name":"Beijing Pediatric Research Institute Department of Otolaryngology, Head and Neck Surgery Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0b013e3181ec6afe"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980518)77:3<219::AID-AJMG6>3.0.CO;2-K"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.1.26"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1300"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/429417"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13048-017-0312-9","article-title":"Cytochrome P450 oxidoreductase deficiency caused by R457H mutation in POR gene in Chinese: case report and literature review","volume":"10","author":"Bai Y","year":"2017","journal-title":"J Ovarian 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