Cargando…
Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure
A large proportion of patients with idiopathic spermatogenic failure (SPGF; oligozoospermia or nonobstructive azoospermia [NOA]) do not receive a diagnosis despite an extensive diagnostic workup. Recent evidence has shown that the etiology remains undefined in up to 75% of these patients. A number o...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer - Medknow
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831827/ https://www.ncbi.nlm.nih.gov/pubmed/32655042 http://dx.doi.org/10.4103/aja.aja_25_20 |
_version_ | 1783641701347229696 |
---|---|
author | Cannarella, Rossella Condorelli, Rosita A Paolacci, Stefano Barbagallo, Federica Guerri, Giulia Bertelli, Matteo La Vignera, Sandro Calogero, Aldo E |
author_facet | Cannarella, Rossella Condorelli, Rosita A Paolacci, Stefano Barbagallo, Federica Guerri, Giulia Bertelli, Matteo La Vignera, Sandro Calogero, Aldo E |
author_sort | Cannarella, Rossella |
collection | PubMed |
description | A large proportion of patients with idiopathic spermatogenic failure (SPGF; oligozoospermia or nonobstructive azoospermia [NOA]) do not receive a diagnosis despite an extensive diagnostic workup. Recent evidence has shown that the etiology remains undefined in up to 75% of these patients. A number of genes involved in germ-cell proliferation, spermatocyte meiotic divisions, and spermatid development have been called into play in the pathogenesis of idiopathic oligozoospermia or NOA. However, this evidence mainly comes from case reports. Therefore, this study was undertaken to identify the molecular causes of SPGF. To accomplish this, 15 genes (USP9Y, NR5A1, KLHL10, ZMYND15, PLK4, TEX15, TEX11, MEIOB, SOHLH1, HSF2, SYCP3, TAF4B, NANOS1, SYCE1, and RHOXF2) involved in idiopathic SPGF were simultaneously analyzed in a cohort of 25 patients with idiopathic oligozoospermia or NOA, accurately selected after a thorough diagnostic workup. After next-generation sequencing (NGS) analysis, we identified the presence of rare variants in the NR5A1 and TEX11 genes with a pathogenic role in 3/25 (12.0%) patients. Seventeen other different variants were identified, and among them, 13 have never been reported before. Eleven out of 17 variants were likely pathogenic and deserve functional or segregation studies. The genes most frequently mutated were MEIOB, followed by USP9Y, KLHL10, NR5A1, and SOHLH1. No alterations were found in the SYCP3, TAF4B, NANOS1, SYCE1, or RHOXF2 genes. In conclusion, NGS technology, by screening a specific custom-made panel of genes, could help increase the diagnostic rate in patients with idiopathic oligozoospermia or NOA. |
format | Online Article Text |
id | pubmed-7831827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Wolters Kluwer - Medknow |
record_format | MEDLINE/PubMed |
spelling | pubmed-78318272021-02-01 Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure Cannarella, Rossella Condorelli, Rosita A Paolacci, Stefano Barbagallo, Federica Guerri, Giulia Bertelli, Matteo La Vignera, Sandro Calogero, Aldo E Asian J Androl Original Article A large proportion of patients with idiopathic spermatogenic failure (SPGF; oligozoospermia or nonobstructive azoospermia [NOA]) do not receive a diagnosis despite an extensive diagnostic workup. Recent evidence has shown that the etiology remains undefined in up to 75% of these patients. A number of genes involved in germ-cell proliferation, spermatocyte meiotic divisions, and spermatid development have been called into play in the pathogenesis of idiopathic oligozoospermia or NOA. However, this evidence mainly comes from case reports. Therefore, this study was undertaken to identify the molecular causes of SPGF. To accomplish this, 15 genes (USP9Y, NR5A1, KLHL10, ZMYND15, PLK4, TEX15, TEX11, MEIOB, SOHLH1, HSF2, SYCP3, TAF4B, NANOS1, SYCE1, and RHOXF2) involved in idiopathic SPGF were simultaneously analyzed in a cohort of 25 patients with idiopathic oligozoospermia or NOA, accurately selected after a thorough diagnostic workup. After next-generation sequencing (NGS) analysis, we identified the presence of rare variants in the NR5A1 and TEX11 genes with a pathogenic role in 3/25 (12.0%) patients. Seventeen other different variants were identified, and among them, 13 have never been reported before. Eleven out of 17 variants were likely pathogenic and deserve functional or segregation studies. The genes most frequently mutated were MEIOB, followed by USP9Y, KLHL10, NR5A1, and SOHLH1. No alterations were found in the SYCP3, TAF4B, NANOS1, SYCE1, or RHOXF2 genes. In conclusion, NGS technology, by screening a specific custom-made panel of genes, could help increase the diagnostic rate in patients with idiopathic oligozoospermia or NOA. Wolters Kluwer - Medknow 2020-07-10 /pmc/articles/PMC7831827/ /pubmed/32655042 http://dx.doi.org/10.4103/aja.aja_25_20 Text en Copyright: ©The Author(s)(2020) http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Cannarella, Rossella Condorelli, Rosita A Paolacci, Stefano Barbagallo, Federica Guerri, Giulia Bertelli, Matteo La Vignera, Sandro Calogero, Aldo E Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure |
title | Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure |
title_full | Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure |
title_fullStr | Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure |
title_full_unstemmed | Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure |
title_short | Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure |
title_sort | next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831827/ https://www.ncbi.nlm.nih.gov/pubmed/32655042 http://dx.doi.org/10.4103/aja.aja_25_20 |
work_keys_str_mv | AT cannarellarossella nextgenerationsequencingtowardanincreaseinthediagnosticyieldinpatientswithapparentlyidiopathicspermatogenicfailure AT condorellirositaa nextgenerationsequencingtowardanincreaseinthediagnosticyieldinpatientswithapparentlyidiopathicspermatogenicfailure AT paolaccistefano nextgenerationsequencingtowardanincreaseinthediagnosticyieldinpatientswithapparentlyidiopathicspermatogenicfailure AT barbagallofederica nextgenerationsequencingtowardanincreaseinthediagnosticyieldinpatientswithapparentlyidiopathicspermatogenicfailure AT guerrigiulia nextgenerationsequencingtowardanincreaseinthediagnosticyieldinpatientswithapparentlyidiopathicspermatogenicfailure AT bertellimatteo nextgenerationsequencingtowardanincreaseinthediagnosticyieldinpatientswithapparentlyidiopathicspermatogenicfailure AT lavignerasandro nextgenerationsequencingtowardanincreaseinthediagnosticyieldinpatientswithapparentlyidiopathicspermatogenicfailure AT calogeroaldoe nextgenerationsequencingtowardanincreaseinthediagnosticyieldinpatientswithapparentlyidiopathicspermatogenicfailure |