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Co-Occurrence of a Pathogenic HSD3B2 Variant and a Duplication on 10q22.3-q23.2 Detected in Newborn Twins with Salt-Wasting Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by enzyme deficiencies required for cortisol biosynthesis in the adrenal cortex. The majority of CAH are due to the deficiency of the 21-hydroxylase enzyme, while 3β-hydroxysteroid dehydrogenase type 2 deficiency...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777535/ https://www.ncbi.nlm.nih.gov/pubmed/36553457 http://dx.doi.org/10.3390/genes13122190 |
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author | Mellone, Simona Bertelli, Enrica Roviglione, Barbara Vurchio, Denise Ronzani, Sara Secco, Andrea Felici, Enrico Strozzi, Mariachiara Martina Schena, Federico Giordano, Mara |
author_facet | Mellone, Simona Bertelli, Enrica Roviglione, Barbara Vurchio, Denise Ronzani, Sara Secco, Andrea Felici, Enrico Strozzi, Mariachiara Martina Schena, Federico Giordano, Mara |
author_sort | Mellone, Simona |
collection | PubMed |
description | Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by enzyme deficiencies required for cortisol biosynthesis in the adrenal cortex. The majority of CAH are due to the deficiency of the 21-hydroxylase enzyme, while 3β-hydroxysteroid dehydrogenase type 2 deficiency accounts for less than five percent of all CAH cases. We report two Moroccan twins from a spontaneous triplet pregnancy. The 46,XY newborn exhibited a disorder of sexual differentiation (DSD) with hypo virilization, while the 46,XX newborn had normal female external genitalia. In the first week of life, they showed hyponatremia and primary adrenal insufficiency with a slight 17OHP elevation and increased DHEAS and renin levels. The aCGH-SNP analysis disclosed a 8.36 Mb long contiguous stretch of homozygosity (LCSH) on chromosome 1p13.2-p11.2 including the candidate HSD3B2 gene, a LCSH of 7.3 Mb on 14q31.1-q32.11, and a 7 Mb duplication on 10q22.3-q23.2. Clinical exome sequencing revealed the biallelic c.969T > G (p.Asn323Lys) HSD3B2, likely pathogenic, variant in both of the affected twins. This case emphasizes the importance of a prompt molecular diagnosis performed through the combination of aCGH and clinical exome, both for establishment of correct therapy and for follow-up, as the newborns also carry a genomic rearrangement with possible clinical implications. |
format | Online Article Text |
id | pubmed-9777535 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97775352022-12-23 Co-Occurrence of a Pathogenic HSD3B2 Variant and a Duplication on 10q22.3-q23.2 Detected in Newborn Twins with Salt-Wasting Congenital Adrenal Hyperplasia Mellone, Simona Bertelli, Enrica Roviglione, Barbara Vurchio, Denise Ronzani, Sara Secco, Andrea Felici, Enrico Strozzi, Mariachiara Martina Schena, Federico Giordano, Mara Genes (Basel) Case Report Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by enzyme deficiencies required for cortisol biosynthesis in the adrenal cortex. The majority of CAH are due to the deficiency of the 21-hydroxylase enzyme, while 3β-hydroxysteroid dehydrogenase type 2 deficiency accounts for less than five percent of all CAH cases. We report two Moroccan twins from a spontaneous triplet pregnancy. The 46,XY newborn exhibited a disorder of sexual differentiation (DSD) with hypo virilization, while the 46,XX newborn had normal female external genitalia. In the first week of life, they showed hyponatremia and primary adrenal insufficiency with a slight 17OHP elevation and increased DHEAS and renin levels. The aCGH-SNP analysis disclosed a 8.36 Mb long contiguous stretch of homozygosity (LCSH) on chromosome 1p13.2-p11.2 including the candidate HSD3B2 gene, a LCSH of 7.3 Mb on 14q31.1-q32.11, and a 7 Mb duplication on 10q22.3-q23.2. Clinical exome sequencing revealed the biallelic c.969T > G (p.Asn323Lys) HSD3B2, likely pathogenic, variant in both of the affected twins. This case emphasizes the importance of a prompt molecular diagnosis performed through the combination of aCGH and clinical exome, both for establishment of correct therapy and for follow-up, as the newborns also carry a genomic rearrangement with possible clinical implications. MDPI 2022-11-23 /pmc/articles/PMC9777535/ /pubmed/36553457 http://dx.doi.org/10.3390/genes13122190 Text en © 2022 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 Mellone, Simona Bertelli, Enrica Roviglione, Barbara Vurchio, Denise Ronzani, Sara Secco, Andrea Felici, Enrico Strozzi, Mariachiara Martina Schena, Federico Giordano, Mara Co-Occurrence of a Pathogenic HSD3B2 Variant and a Duplication on 10q22.3-q23.2 Detected in Newborn Twins with Salt-Wasting Congenital Adrenal Hyperplasia |
title | Co-Occurrence of a Pathogenic HSD3B2 Variant and a Duplication on 10q22.3-q23.2 Detected in Newborn Twins with Salt-Wasting Congenital Adrenal Hyperplasia |
title_full | Co-Occurrence of a Pathogenic HSD3B2 Variant and a Duplication on 10q22.3-q23.2 Detected in Newborn Twins with Salt-Wasting Congenital Adrenal Hyperplasia |
title_fullStr | Co-Occurrence of a Pathogenic HSD3B2 Variant and a Duplication on 10q22.3-q23.2 Detected in Newborn Twins with Salt-Wasting Congenital Adrenal Hyperplasia |
title_full_unstemmed | Co-Occurrence of a Pathogenic HSD3B2 Variant and a Duplication on 10q22.3-q23.2 Detected in Newborn Twins with Salt-Wasting Congenital Adrenal Hyperplasia |
title_short | Co-Occurrence of a Pathogenic HSD3B2 Variant and a Duplication on 10q22.3-q23.2 Detected in Newborn Twins with Salt-Wasting Congenital Adrenal Hyperplasia |
title_sort | co-occurrence of a pathogenic hsd3b2 variant and a duplication on 10q22.3-q23.2 detected in newborn twins with salt-wasting congenital adrenal hyperplasia |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777535/ https://www.ncbi.nlm.nih.gov/pubmed/36553457 http://dx.doi.org/10.3390/genes13122190 |
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