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

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 pict...

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Autores principales: Matusik, Pawel, Gach, Agnieszka, Zajdel-Cwynar, Olimpia, Pinkier, Iwona, Kudela, Grzegorz, Gawlik, Aneta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295740/
https://www.ncbi.nlm.nih.gov/pubmed/34281122
http://dx.doi.org/10.3390/ijerph18137186
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author Matusik, Pawel
Gach, Agnieszka
Zajdel-Cwynar, Olimpia
Pinkier, Iwona
Kudela, Grzegorz
Gawlik, Aneta
author_facet Matusik, Pawel
Gach, Agnieszka
Zajdel-Cwynar, Olimpia
Pinkier, Iwona
Kudela, Grzegorz
Gawlik, Aneta
author_sort Matusik, Pawel
collection PubMed
description 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.
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spelling pubmed-82957402021-07-23 A Novel Intronic Splice—Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development Matusik, Pawel Gach, Agnieszka Zajdel-Cwynar, Olimpia Pinkier, Iwona Kudela, Grzegorz Gawlik, Aneta Int J Environ Res Public Health Case Report 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. MDPI 2021-07-05 /pmc/articles/PMC8295740/ /pubmed/34281122 http://dx.doi.org/10.3390/ijerph18137186 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Matusik, Pawel
Gach, Agnieszka
Zajdel-Cwynar, Olimpia
Pinkier, Iwona
Kudela, Grzegorz
Gawlik, Aneta
A Novel Intronic Splice—Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development
title A Novel Intronic Splice—Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development
title_full A Novel Intronic Splice—Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development
title_fullStr A Novel Intronic Splice—Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development
title_full_unstemmed A Novel Intronic Splice—Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development
title_short A Novel Intronic Splice—Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development
title_sort novel intronic splice—site mutation of the cyp11a1 gene linked to adrenal insufficiency with 46,xy disorder of sex development
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295740/
https://www.ncbi.nlm.nih.gov/pubmed/34281122
http://dx.doi.org/10.3390/ijerph18137186
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