P450c17 deficiency: clinical and molecular characterization of six patients
Open accessAbstract
CONTEXT: The characteristics of P450c17 deficiency include 46,XY disorder of sex development, hypertension, hypokalemia, and lack of pubertal development. OBJECTIVE: To better understand this rare enzymatic deficiency, we analyzed the CYP17A1 gene in six affected patients. DESIGN AND PATIENTS: We examined six patients, five 46,XY, and one 46,XX (age 9-29 yr) with complete lack of masculinization (female infantile external genitalia, no uterus) and delayed puberty, respectively, and different degrees of hypertension. MAIN OUTCOME MEASUREMENTS: Genotype-phenotype correlation was measured. RESULTS: Four homozygote mutations were identified by direct sequencing of the CYP17A1 gene corresponding to an alanin 302-proline (A302P) exchange; the loss of lysine 327 (K327del); the deletion of glutamate 331 (E331del); and the replacement of arginine 416 with a histidine (R416H). Both P450c17 activities were abolished in all the mutant proteins, except one, when expressed in COS1 cells. The E331del-mutated P450c17 retained 17alpha-hydroxylase activity. The mutant proteins were normally expressed, suggesting that the loss of enzymatic activity is not due to defects of synthesis, stability, or localization of P450c17 proteins. CONCLUSION: These studies confirm lack of masculinization in 46,XY individuals as the pathognomic sign of the complete P450c17 deficiency. In XX individuals P450c17 deficiency should be considered in cases of delayed puberty. Age of onset and the severity of hypertension do not seem to be constant. Careful examination of long-term follow-ups in two of our patients suggested to us that estrogen treatment in P450c17-deficient patients might worsen the enzymatic defect, leading to aggravation of the hypertension.
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More than 50 distinct mutations causing 17α-hydroxylase deficiency have been identified.
“More than 50 distinct mutations causing 17␣-hydroxylase deficiency have been identified (267, 268).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [268]
The opening section (p. 1) says CYP17A1 mutations can cause 17α-hydroxylase deficiency, and the Results report four mutations identified in six patients. Neither those passages nor the passages found by searching for the claimed total state that more than 50 distinct causative mutations had been identified. The paper’s 50 control subjects (Mutation analysis, p. 2) are not a mutation count. (LLM, conf=0.82)
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The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders
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- Authors
- Rosa, S., Duff, C., Meyer, M., Lang-Muritano, M., Balercia, G., Boscaro, M., Kemal Topaloglu, A., Mioni, R., Fallo, F., Zuliani, L., Mantero, F., Schoenle, E. J., & Biason-Lauber, A.
- Affiliations
- University Children's Hospital Zurich (CH)
- University Children’s Hospital Zürich (S.R., C.D., M.M., M.L.-M., E.J.S., A.B.-L.), 8032 Zürich, Switzerland
- Azienda Ospedaliero-Universitaria delle Marche (IT)
- Division of Pediatric Endocrinology and Metabolism (A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey
- University of Padua (IT)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2007-03-01
- Volume
- 92
- Issue
- 3
- Pages
- 1000-1007
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2114642500
- Semantic Scholar
- d259e6eaec4e075fd8c0defa2d26ce64b7ae6feb
- Cited by
- 71
- References
- 26
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 2
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (other-oa)
- 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 › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Keywords
- 17-hydroxylase deficiency, 46,XY disorders of sex development, 46,XX disorders of sex development, delayed puberty, hypertension, hypokalemia, genotype-phenotype correlation, estrogen therapy
- MeSH terms
- Adolescent, Adult, Animals, Blood Pressure, Chlorocebus aethiops, Child, DNA Mutational Analysis, Gonadal Dysgenesis, 46,XY, Humans, Mutation, Progesterone, Radiography, Steroid 17-alpha-Hydroxylase, Transfection, Genes, Reporter, COS Cells, Gonadal Dysgenesis, 46,XX
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