{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:01:30Z","timestamp":1769158890017,"version":"3.49.0"},"reference-count":16,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"Narodowym Centrum Nauki","doi-asserted-by":"publisher","award":["2014\/13\/B\/NZ5\/03102"],"award-info":[{"award-number":["2014\/13\/B\/NZ5\/03102"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>A novel CYP11A1: c.1236 + 5G &gt; A was identified, expanding the mutation spectrum of the congenital adrenal insufficiency with 46,XY sex reversal. In a now 17-year-old girl delivered full-term (G2P2, parents unrelated), adrenal failure was diagnosed in the first year of life based on clinical picture of acute adrenal crisis with vomiting, dehydration, weight loss, hypotension, and electrolyte disturbances. At the time, hormonal tests revealed primary adrenocortical insufficiency and steroid profiles showed lack of products of steroidogenesis, and since then the patient has been treated with substitution doses of hydrocortisone and fludrocortisone. At the age of 14, considering the absence of puberty symptoms, extended diagnostic tests revealed elevated LH levels (26.5 mIU\/mL) with pre-puberty FSH levels (4.9 mIU\/mL), low estradiol (28 pmol\/L), testosterone (&lt;2.5 ng\/mL), and extremely high levels of ACTH (4961 pg\/mL). A cytogenetic study revealed a 46 XY karyotype. A molecular examination confirmed the missense mutation and a novel splice-site mutation of CYP11A1 gene. Compound heterozygosity for the CYP11A1 gene with a known pathogenic variant in one allele and a novel splice site mutation in the second allele is most probably responsible for congenital adrenal insufficiency with 46,XY sex reversal. We discuss the necessity of cytogenetic test in the case of early onset of adrenal failure in the absence of steroidogenesis metabolites in the steroid profile.<\/jats:p>","DOI":"10.3390\/ijerph18137186","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T22:02:04Z","timestamp":1625522524000},"page":"7186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Novel Intronic Splice\u2014Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8943-7051","authenticated-orcid":false,"given":"Pawel","family":"Matusik","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Pediatric Endocrinology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-5797","authenticated-orcid":false,"given":"Agnieszka","family":"Gach","sequence":"additional","affiliation":[{"name":"Department of Genetics, Polish Mother\u2019s Memorial Hospital Research Institute, 93-338 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olimpia","family":"Zajdel-Cwynar","sequence":"additional","affiliation":[{"name":"Upper-Silesian Child\u2019s Health Centre, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iwona","family":"Pinkier","sequence":"additional","affiliation":[{"name":"Department of Genetics, Polish Mother\u2019s Memorial Hospital Research Institute, 93-338 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6743-9833","authenticated-orcid":false,"given":"Grzegorz","family":"Kudela","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Urology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9309-4741","authenticated-orcid":false,"given":"Aneta","family":"Gawlik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Endocrinology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1194\/jlr.R016675","article-title":"Early steps in steroidogenesis: Intracellular cholesterol trafficking Thematic Review Series: Genetics of Human Lipid Diseases","volume":"52","author":"Miller","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/0960-0760(92)90307-5","article-title":"Steroidogenic enzymes: Structure, function, and role in regulation of steroid hormone biosynthesis","volume":"43","author":"Hanukoglu","year":"1992","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3808","DOI":"10.1210\/jcem.87.8.8763","article-title":"Compound heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A) cause congenital adrenal insufficiency in humans","volume":"87","author":"Katsumata","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","first-page":"231","article-title":"Splicing mutations in human genetic disorders: Examples, detection, and confirmation","volume":"59","author":"Abramowicz","year":"2018","journal-title":"J. Appl. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1210\/jc.2004-1059","article-title":"Homozygous Disruption of P450 Side-Chain Cleavage (CYP11A1) Is Associated with Prematurity, Complete 46,XY Sex Reversal, and Severe Adrenal Failure","volume":"90","author":"Hiort","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1210\/jc.2007-2330","article-title":"Severe Combined Adrenal and Gonadal Deficiency Caused by Novel Mutations in the Cholesterol Side Chain Cleavage Enzyme, P450scc","volume":"93","author":"Kim","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1210\/jc.2005-2230","article-title":"Homozygous Mutation of P450 Side-Chain Cleavage Enzyme Gene (CYP11A1) in 46, XY Patient with Adrenal Insufficiency, Complete Sex Reversal, and Agenesis of Corpus Callosum","volume":"91","author":"Katsumata","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1210\/jc.2008-1118","article-title":"A Novel Homozygous Mutation in CYP11A1 Gene Is Associated with Late-Onset Adrenal Insufficiency and Hypospadias in a 46,XY Patient","volume":"94","author":"Rubtsov","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1210\/jc.2010-1828","article-title":"Partial Defect in the Cholesterol Side-Chain Cleavage Enzyme P450scc (CYP11A1) Resembling Nonclassic Congenital Lipoid Adrenal Hyperplasia","volume":"96","author":"Sahakitrungruang","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1210\/jcem.86.8.7748","article-title":"Heterozygous Mutation in the Cholesterol Side Chain Cleavage Enzyme (P450scc) Gene in a Patient with 46,XY Sex Reversal and Adrenal Insufficiency","volume":"86","author":"Tajima","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1056\/NEJM199612193352503","article-title":"The Pathophysiology and Genetics of Congenital Lipoid Adrenal Hyperplasia","volume":"335","author":"Bose","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1093\/hmg\/6.4.571","article-title":"Analysis of the Steroidogenic Acute Regulatory Protein (StAR) Gene in Japanese Patients with Congenital Lipoid Adrenal Hyperplasia","volume":"6","author":"Nakae","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","first-page":"3636","article-title":"Mutations in the Steroidogenic Acute Regulatory Protein (StAR) in Six Patients with Congenital Lipoid Adrenal Hyperplasia","volume":"85","author":"Bose","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jsbmb.2014.11.010","article-title":"Novel activities of CYP11A1 and their potential physiological significance","volume":"151","author":"Slominski","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_15","first-page":"1","article-title":"A Novel Homozygous Mutation in CYP11A1 Gene is Associated with Severe Adrenal Insufficiency in 46, XX Patient","volume":"31","author":"Kara","year":"2020","journal-title":"Fetal Pediatr. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Splittst\u00f6sser, V., Schreiner, F., Gohlke, B., Welzel, M., Holterhus, P.M., and Woelfle, J. (2019). A novel mutation of the StAR gene with congenital adrenal hyperplasia and its association with heterochromia iridis: A case report. BMC Endocr. 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