A Novel Intronic Splice—Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development

Pawel Matusik, Agnieszka Gach, Olimpia Zajdel-Cwynar, Iwona Pinkier, Grzegorz Kudela and Aneta Gawlik
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Pawel Matusik: Department of Pediatrics and Pediatric Endocrinology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
Agnieszka Gach: Department of Genetics, Polish Mother’s Memorial Hospital Research Institute, 93-338 Lodz, Poland
Olimpia Zajdel-Cwynar: Upper-Silesian Child’s Health Centre, 40-752 Katowice, Poland
Iwona Pinkier: Department of Genetics, Polish Mother’s Memorial Hospital Research Institute, 93-338 Lodz, Poland
Grzegorz Kudela: Department of Pediatric Surgery and Urology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
Aneta Gawlik: Department of Pediatrics and Pediatric Endocrinology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland

IJERPH, 2021, vol. 18, issue 13, 1-7

Abstract: A novel CYP11A1 : c.1236 + 5G > 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 (<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.

Keywords: CYP11A1 gene; disorder of sex development (DSD); congenital adrenal hyperplasia (CAH); novel mutation (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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