Cytochrome P450 oxidoreductase deficiency caused by a novel mutation in the POR gene in two siblings: case report and literature review
Abstract
Introduction P450 oxidoreductase (POR) deficiency is a rare form of congenital adrenal hyperplasia. In both genders, it can lead to ambiguous genitalia, impaired steroidogenesis, and skeletal findings similar to those of Antley-Bixler syndrome. Cases We describe two cases of POR deficiency. The first case was an 8.5-year-old girl who was admitted to our clinic due to ambiguous genitalia. Karyotype was 46, XX. There were mild dysmorphic facial findings and mild metacarpophalangeal joint deformity. The patient's basal cortisol and ACTH levels were normal, while 17-hydroxyprogesterone (17OHP) levels were high. Peak cortisol response to the ACTH stimulation test was found to be insufficient. Our second case, a sibling of the first case, was admitted for routine checkup at the age of 15 months. As in our first case, there were dysmorphic facial findings and metacarpophalangeal joint deformity. The genital structure was normal. Karyotype was 46, XY. Basal cortisol and ACTH levels were normal, while 17OHP level was slightly high. Peak cortisol response to the ACTH stimulation test was found to be insufficient. Based on our findings, POR deficiency was considered in both of these cases and NM_000941.3:c.929_937delTCTCGGACT(p.Ile310_Ser313delinsThr) (homozygous) mutation was detected in the POR gene that had not previously been described. Conclusion We detected a novel variant in the POR gene in two sibling cases with adrenal insufficiency, dysmorphic face, and mild skeletal findings.…
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Glucocorticoid biosynthesis in the adrenal glands is impaired due to deficiencies in CYP21A2 and CYP17A1 activity, predisposing PORD patients to adrenal crisis under stressful conditions such as infection, trauma, or surgery.
“However, glucocorticoid biosynthesis in the adrenal glands is impaired due to deficiencies in CYP21A2 and CYP17A1 activity, patients to adrenal crisis under stressful conditions such as infection, trauma, or surgery (42, 57).”
From Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel mutation and systematic review (2026) · cites this paper as [42]
Abnormal sexual development is generally more pronounced in female than in male patients with PORD.
“Multiple studies consistently report that abnormal sexual development is generally more pronounced in female than in male patients with PORD (21, 42).”
From Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel mutation and systematic review (2026) · cites this paper as [42]
Most patients with PORD exhibit skeletal deformities resembling Antley-Bixler syndrome, such as craniosynostosis, midface hypoplasia, arachnodactyly, elbow synostosis, and femoral bowing.
“Most patients with PORD exhibit skeletal deformities resembling Antley-Bixler syndrome, such as craniosynostosis, midface hypoplasia, arachnodactyly, elbow synostosis, and femoral bowing (1, 3, 42, 57).”
From Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel mutation and systematic review (2026) · cites this paper as [42]
Cites
Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome
Flück, C. E., Tajima, T., Pandey, A. V., Arlt, W., Okuhara, K., Verge, C. F., Jabs, E. W., Mendonça, B. B., Fujieda, K., & Miller, W. L. (2004) · Nature Genetics · doi:10.1038/ng1300 · Cited by 509 · see citing works
The backdoor pathway to dihydrotestosterone
Auchus, R. J. (2004) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2004.09.004 · Cited by 347 · see citing works
Huang, N., Pandey, A. V., Agrawal, V., Reardon, W., Lapunzina, P. D., Mowat, D., Jabs, E. W., Vliet, G. V., Sack, J., Flück, C. E., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/429417 · Cited by 336 · see citing works
Genotype-Phenotype Analysis in Congenital Adrenal Hyperplasia due to P450 Oxidoreductase Deficiency
Krone, N., Reisch, N., Idkowiak, J., Dhir, V., Ivison, H. E., Hughes, B. A., Rose, I. T., O'Neil, D. M., Vijzelaar, R., Smith, M. J., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0640 · Cited by 163 · see citing works
Fukami, M., Horikawa, R., Nagai, T., Tanaka, T., Naiki, Y., Sato, N., Okuyama, T., Nakai, H., Soneda, S., Tachibana, K., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0810 · Cited by 155 · see citing works
Homma, K., Hasegawa, T., Nagai, T., Adachi, M., Horikawa, R., Fujiwara, I., Tajima, T., Takeda, R., Fukami, M., & Ogata, T. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2460 · Cited by 153 · see citing works
Peterson, R. E., Imperato-McGinley, J., Gautier, T., & Shackleton, C. (1985) · New England Journal of Medicine · doi:10.1056/nejm198511073131903 · Cited by 148 · see citing works
Modulation of human CYP19A1 activity by mutant NADPH P450 oxidoreductase
Pandey, A. V., Kempná, P., Hofer, G., Mullis, P. E., & Flück, C. E. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0245 · Cited by 132 · see citing works
Adachi, M., Tachibana, K., Asakura, Y., Yamamoto, T., Hanaki, K., & Oka, A. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30169 · Cited by 110 · see citing works
Shackleton, C., Marcos, J., Arlt, W., & Hauffa, B. P. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30171 · Cited by 104 · see citing works
Hershkovitz, E., Parvari, R., Wudy, S. A., Hartmann, M. F., Gomes, L. G., Loewental, N., & Miller, W. L. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0051 · Cited by 95 · see citing works
P450 Oxidoreductase deficiency: Analysis of mutations and polymorphisms
Burkhard, F. Z., Parween, S., Udhane, S. S., Flück, C. E., & Pandey, A. V. (2017) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.04.003 · Cited by 79 · see citing works
P450 oxidoreductase deficiency
Miller, W. L., Huang, N., Flück, C. E., & Pandey, A. V. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17344-3 · Cited by 37 · see citing works
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Congenital adrenal hyperplasia due to P450 oxidoreductase deficiency
Zhang, J., Woo, K. L., Hai, Y., Wang, S., Lin, Y., Huang, Y., Peng, X., Wu, H., Zhang, S., Yan, L., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1020880 · Cited by 10 · see citing works
Zhang, C., Zhao, Z., Du, Y., Huang, Q., Liu, Y., Fu, G., & Xu, J. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1791297
“Most patients with PORD exhibit skeletal deformities resembling Antley-Bixler syndrome, such as craniosynostosis, midface hypoplasia, arachnodactyly, elbow synostosis, and femoral bowing (1, 3, 42, 57).”
- Authors
- Unal, E., Demiral, M., Yıldırım, R., Taş, F. F., Ceylaner, S., & Özbek, M. N.
- Affiliations
- Diyarbakır Gazi Yaşargil Eğitim ve Araştırma Hastanesi (TR)
- Intergen (Turkey) (TR)
- Venue
- Hormones
- Published
- 2020-10-29
- Volume
- 20
- Issue
- 2
- Pages
- 293-298
- ISSN
- 1109-3099 (ISSN-L)
- 2520-8721
- OpenAlex
- W3097401773
- Cited by
- 12
- References
- 13
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 2
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- HORMONES (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- P450 oxidoreductase deficiency, POR gene, novel mutations, congenital adrenal hyperplasia, ambiguous genitalia, adrenal insufficiency, 17-hydroxyprogesterone, ACTH stimulation test, facial dysmorphism, Antley-Bixler syndrome, steroidogenesis, siblings
- MeSH terms
- Adrenal Hyperplasia, Congenital, Adrenocorticotropic Hormone, Child, Female, Humans, Hydrocortisone, Infant, Male, Mutation, Phenotype, Siblings, Antley-Bixler Syndrome Phenotype
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