Novel phenotypes and genotypes in Antley-Bixler syndrome caused by cytochrome P450 oxidoreductase deficiency: based on t
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(2019) 14:299
RESEARCH
Open Access
Novel phenotypes and genotypes in Antley-Bixler syndrome caused by cytochrome P450 oxidoreductase deficiency: based on the first cohort of Chinese children Lijun Fan1,2†, Xiaoya Ren1,2†, Yanning Song1,2, Chang Su1,2, Junfen Fu3 and Chunxiu Gong1,2*
Abstract Background: 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. Methods: 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. Results: Eight patients, aged 6 months–17.8 years, 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 POR. The most prevalent variant was p.R457H (8/16). The hydrocortisone dosages of patients differed because of variable degrees of adrenal insufficiency. Conclusions: 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. Keywords: Antley-Bixler syndrome, Cytochrome P450 oxidoreductase deficiency, Disorder of sex development, Congenital adrenal hyperplasia, POR gene
* Correspondence: [email protected] † Lijun Fan and Xiaoya Ren should be considered joint first author. 1 Department of Endocrinology, Genetics, Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 56# Nan Lishi Rd, West District, Beijing 100045, China 2 Beijing Key Laboratory for Genetics of Birth Defects, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 56# Nan Lishi Rd, West District, Beijing 100045, China Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to t
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