A Case of Salt-Wasting Congenital Adrenal Hyperplasia Caused by a Rare Intronic Variant in the CYP21A2 Gene.
| Title: | A Case of Salt-Wasting Congenital Adrenal Hyperplasia Caused by a Rare Intronic Variant in the CYP21A2 Gene. |
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| Authors: | Antysheva Z; Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia.; Moscow Center for Advanced Studies, 123592 Moscow, Russia.; Esibov A; Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia.; Moscow Center for Advanced Studies, 123592 Moscow, Russia.; Avsievich E; Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia.; Moscow Center for Advanced Studies, 123592 Moscow, Russia.; Moscow Clinical Scientific Center n.a. A.S. Loginov, 111123 Moscow, Russia.; Petriaikina E; Federal State Budgetary Institution «Centre for Strategic Planning and Management of Biomedical Health Risks» of the Federal medical and biological agency (Centre for Strategic Planning of the Federal medical and biological agency), 119121 Moscow, Russia.; Yudin V; Federal State Budgetary Institution «Centre for Strategic Planning and Management of Biomedical Health Risks» of the Federal medical and biological agency (Centre for Strategic Planning of the Federal medical and biological agency), 119121 Moscow, Russia.; Keskinov A; Federal State Budgetary Institution «Centre for Strategic Planning and Management of Biomedical Health Risks» of the Federal medical and biological agency (Centre for Strategic Planning of the Federal medical and biological agency), 119121 Moscow, Russia.; Yudin S; Federal State Budgetary Institution «Centre for Strategic Planning and Management of Biomedical Health Risks» of the Federal medical and biological agency (Centre for Strategic Planning of the Federal medical and biological agency), 119121 Moscow, Russia.; Svetlichnyy D; Federal State Budgetary Institution «Centre for Strategic Planning and Management of Biomedical Health Risks» of the Federal medical and biological agency (Centre for Strategic Planning of the Federal medical and biological agency), 119121 Moscow, Russia.; Krupinova J; Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia.; Moscow Center for Advanced Studies, 123592 Moscow, Russia.; Moscow Clinical Scientific Center n.a. A.S. Loginov, 111123 Moscow, Russia.; Ivashechkin A; Federal State Budgetary Institution «Centre for Strategic Planning and Management of Biomedical Health Risks» of the Federal medical and biological agency (Centre for Strategic Planning of the Federal medical and biological agency), 119121 Moscow, Russia.; Katsaran Y; Federal State Budgetary Institution «Centre for Strategic Planning and Management of Biomedical Health Risks» of the Federal medical and biological agency (Centre for Strategic Planning of the Federal medical and biological agency), 119121 Moscow, Russia.; Woroncow M; Faculty of Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia.; Skvortsova V; The Federal Medical Biological Agency (FMBA of Russia), 123182 Moscow, Russia.; Bogdanov V; Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia.; Moscow Center for Advanced Studies, 123592 Moscow, Russia.; Volchkov P; Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia.; Moscow Center for Advanced Studies, 123592 Moscow, Russia.; Moscow Clinical Scientific Center n.a. A.S. Loginov, 111123 Moscow, Russia. |
| Source: | International journal of molecular sciences [Int J Mol Sci] 2025 Jul 11; Vol. 26 (14). Date of Electronic Publication: 2025 Jul 11. |
| Publication Type: | Case Reports; Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, [2000- |
| MeSH Terms: | Adrenal Hyperplasia, Congenital*/genetics ; Adrenal Hyperplasia, Congenital*/diagnosis ; Steroid 21-Hydroxylase*/genetics ; Introns*/genetics ; Mutation*; Humans ; Male ; Child, Preschool |
| Abstract: | This case report describes a novel intronic mutation, CYP21A2:c.738+75C>T (rs1463196531), identified in a 4-year-old male with congenital adrenal insufficiency, and expands the known mutation spectrum associated with this condition. The patient, born full-term to unrelated parents, presented with adrenal failure within the first month of life, characterized by acute adrenal crisis symptoms such as vomiting, dehydration, weight loss, hypotension, and electrolyte imbalances. Hormonal evaluations confirmed primary adrenocortical insufficiency, necessitating ongoing hydrocortisone and fludrocortisone therapy. Using family trio-based amplicon sequencing of the CYP21A2 gene, we identified compound heterozygosity consisting of a full gene deletion and a novel pathogenic intronic mutation. Additionally, analysis of WGS data was performed to rule out pathogenic variants in genes that might lead to a similar phenotype, thereby eliminating the possibility of other genes contributing to the proband's disease. This case demonstrates the potential of using amplicon sequencing in molecular genetic diagnostic testing to detect rare intronic variants in the CYP21A2 gene in cases of early-onset adrenal failure. It also contributes to a better understanding of the genetic basis of congenital adrenal hyperplasia (CAH), which remains a significant autosomal recessive disorder affecting cortisol and aldosterone production, with an incidence of 1 in 10,000 to 1 in 15,000 globally. |
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| Grant Information: | FGFG-2025-0016 Ministry of Science and Higher Education of the Russian Federation; FSMG-2024-0029 Ministry of Science and Higher Education of the Russian Federation |
| Contributed Indexing: | Keywords: CYP21A2; NGS; adrenal insufficiency; amplicon sequencing; congenital adrenal hyperplasia; intronic variant; splicing mutations |
| Substance Nomenclature: | EC 1.14.14.16 (Steroid 21-Hydroxylase); EC 1.14.14.16 (CYP21A2 protein, human) |
| Entry Date(s): | Date Created: 20250729 Date Completed: 20250729 Latest Revision: 20250801 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12294710 |
| DOI: | 10.3390/ijms26146648 |
| PMID: | 40724898 |
| Database: | MEDLINE |
Case Reports; Journal Article