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Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing

Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46, XY Disorders of Sex Development (46, XY DSD). The diagnosis of 46, XY DSD is very challenging and not rarely is confirmed only at older ages, when an affected XY female presents with primary amenorrhea or develops progressive v...

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Autores principales: De Falco, Luigia, Piscopo, Carmelo, D’Angelo, Rossana, Evangelista, Eloisa, Suero, Teresa, Sirica, Roberto, Ruggiero, Raffaella, Savarese, Giovanni, Di Carlo, Antonella, Furino, Giulia, Scarpato, Ciro, Fico, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700836/
https://www.ncbi.nlm.nih.gov/pubmed/34946839
http://dx.doi.org/10.3390/genes12121890
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author De Falco, Luigia
Piscopo, Carmelo
D’Angelo, Rossana
Evangelista, Eloisa
Suero, Teresa
Sirica, Roberto
Ruggiero, Raffaella
Savarese, Giovanni
Di Carlo, Antonella
Furino, Giulia
Scarpato, Ciro
Fico, Antonio
author_facet De Falco, Luigia
Piscopo, Carmelo
D’Angelo, Rossana
Evangelista, Eloisa
Suero, Teresa
Sirica, Roberto
Ruggiero, Raffaella
Savarese, Giovanni
Di Carlo, Antonella
Furino, Giulia
Scarpato, Ciro
Fico, Antonio
author_sort De Falco, Luigia
collection PubMed
description Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46, XY Disorders of Sex Development (46, XY DSD). The diagnosis of 46, XY DSD is very challenging and not rarely is confirmed only at older ages, when an affected XY female presents with primary amenorrhea or develops progressive virilization. The patient described in this paper represents a case of discrepancies between non-invasive prenatal testing (NIPT) and ultrasound based fetal sex determination detected during prenatal screening. Exome sequencing was performed on the cell free fetal DNA (cffDNA), amniotic fluid, and the parents. Libraries were generated according to the manufacturer’s protocols using TruSight One Kits (Illumina Inc., San Diego, CA, USA). Sequencing was carried out on NEXT Seq 500 (Illumina) to mean sequencing depth of at least 100×. A panel of sexual disease genes was used in order to search for a causative variant. The finding of a mutation (c.645 A>T, p.Glu215Asp) in HSD17B3 gene in amniotic fluid as well as in cffDNA and both parents supported the hypothesis of the HSD17B3 deficiency. In conclusion, we used clinical exome sequencing and non-invasive prenatal detection, providing a solution for NIPT of a single-gene disorder. Early genetic diagnoses are useful for patients and clinicians, contribute to clinical knowledge of DSD, and are invaluable for genetic counseling of couples contemplating future pregnancies.
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spelling pubmed-87008362021-12-24 Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing De Falco, Luigia Piscopo, Carmelo D’Angelo, Rossana Evangelista, Eloisa Suero, Teresa Sirica, Roberto Ruggiero, Raffaella Savarese, Giovanni Di Carlo, Antonella Furino, Giulia Scarpato, Ciro Fico, Antonio Genes (Basel) Case Report Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46, XY Disorders of Sex Development (46, XY DSD). The diagnosis of 46, XY DSD is very challenging and not rarely is confirmed only at older ages, when an affected XY female presents with primary amenorrhea or develops progressive virilization. The patient described in this paper represents a case of discrepancies between non-invasive prenatal testing (NIPT) and ultrasound based fetal sex determination detected during prenatal screening. Exome sequencing was performed on the cell free fetal DNA (cffDNA), amniotic fluid, and the parents. Libraries were generated according to the manufacturer’s protocols using TruSight One Kits (Illumina Inc., San Diego, CA, USA). Sequencing was carried out on NEXT Seq 500 (Illumina) to mean sequencing depth of at least 100×. A panel of sexual disease genes was used in order to search for a causative variant. The finding of a mutation (c.645 A>T, p.Glu215Asp) in HSD17B3 gene in amniotic fluid as well as in cffDNA and both parents supported the hypothesis of the HSD17B3 deficiency. In conclusion, we used clinical exome sequencing and non-invasive prenatal detection, providing a solution for NIPT of a single-gene disorder. Early genetic diagnoses are useful for patients and clinicians, contribute to clinical knowledge of DSD, and are invaluable for genetic counseling of couples contemplating future pregnancies. MDPI 2021-11-25 /pmc/articles/PMC8700836/ /pubmed/34946839 http://dx.doi.org/10.3390/genes12121890 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
De Falco, Luigia
Piscopo, Carmelo
D’Angelo, Rossana
Evangelista, Eloisa
Suero, Teresa
Sirica, Roberto
Ruggiero, Raffaella
Savarese, Giovanni
Di Carlo, Antonella
Furino, Giulia
Scarpato, Ciro
Fico, Antonio
Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing
title Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing
title_full Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing
title_fullStr Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing
title_full_unstemmed Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing
title_short Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing
title_sort detection of 46, xy disorder of sex development (dsd) based on plasma cell-free dna and targeted next-generation sequencing
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700836/
https://www.ncbi.nlm.nih.gov/pubmed/34946839
http://dx.doi.org/10.3390/genes12121890
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