Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing
Background: Up to 15% of couples are infertile and male factor infertility accounts for approximately 50% of these cases. Male infertility is a multifactorial pathological condition. The genetic of male infertility is very complex and at least 2000 genes are involved in its etiology. Genetic testing...
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2020-10-01
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author | Rossella Cannarella Vincenza Precone Giulia Guerri Gian Maria Busetto Gian Carlo Di Renzo Sandro Gerli Elena Manara Astrit Dautaj Matteo Bertelli Aldo Eugenio Calogero |
author_facet | Rossella Cannarella Vincenza Precone Giulia Guerri Gian Maria Busetto Gian Carlo Di Renzo Sandro Gerli Elena Manara Astrit Dautaj Matteo Bertelli Aldo Eugenio Calogero |
author_sort | Rossella Cannarella |
collection | DOAJ |
description | Background: Up to 15% of couples are infertile and male factor infertility accounts for approximately 50% of these cases. Male infertility is a multifactorial pathological condition. The genetic of male infertility is very complex and at least 2000 genes are involved in its etiology. Genetic testing by next-generation sequencing (NGS) technologies can be relevant for its diagnostic value in male infertile patients. Therefore, the aim of this study was to implement the diagnostic offer with the use of an NGS panel for the identification of genetic variants. Methods: We developed an NGS gene panel that we used in 22 male infertile patients. The panel consisted of 110 genes exploring the genetic causes of male infertility; namely spermatogenesis failure due to single-gene mutations, central hypogonadism, androgen insensitivity syndrome, congenital hypopituitarism, and primary ciliary dyskinesia. Results: NGS and a subsequent sequencing of the positive pathogenic or likely pathogenic variants, 5 patients (23%) were found to have a molecular defect. In particular, pathogenic variants were identified in <i>TEX11</i>, <i>CCDC39</i>, <i>CHD7</i>, and <i>NR5A1</i> genes. Moreover, 14 variants of unknown significance and 7 novel variants were found that require further functional studies and family segregation. Conclusion: This extended NGS-based diagnostic approach may represent a useful tool for the diagnosis of male infertility. The development of a custom-made gene panel by NGS seems capable of reducing the proportion of male idiopathic infertility. |
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spelling | doaj.art-875c7329d70f49f59a51c3ba1d0f0e872023-11-20T17:11:26ZengMDPI AGLife2075-17292020-10-01101024210.3390/life10100242Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation SequencingRossella Cannarella0Vincenza Precone1Giulia Guerri2Gian Maria Busetto3Gian Carlo Di Renzo4Sandro Gerli5Elena Manara6Astrit Dautaj7Matteo Bertelli8Aldo Eugenio Calogero9Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, ItalyMAGI EUREGIO, 39100 Bolzano, ItalyMAGI’S LAB, 38068 Rovereto, ItalyDepartment of Urology, “Sapienza” University of Rome, Policlinico Umberto I, 00185 Rome, ItalyDepartment of Surgical and Biomedical Sciences, University of Perugia, 06123 Perugia, ItalyDepartment of Surgical and Biomedical Sciences, University of Perugia, 06123 Perugia, ItalyMAGI EUREGIO, 39100 Bolzano, ItalyEBTNA-LAB, Via delle Maioliche, 57/G, 38068 Rovereto, ItalyMAGI EUREGIO, 39100 Bolzano, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, 95124 Catania, ItalyBackground: Up to 15% of couples are infertile and male factor infertility accounts for approximately 50% of these cases. Male infertility is a multifactorial pathological condition. The genetic of male infertility is very complex and at least 2000 genes are involved in its etiology. Genetic testing by next-generation sequencing (NGS) technologies can be relevant for its diagnostic value in male infertile patients. Therefore, the aim of this study was to implement the diagnostic offer with the use of an NGS panel for the identification of genetic variants. Methods: We developed an NGS gene panel that we used in 22 male infertile patients. The panel consisted of 110 genes exploring the genetic causes of male infertility; namely spermatogenesis failure due to single-gene mutations, central hypogonadism, androgen insensitivity syndrome, congenital hypopituitarism, and primary ciliary dyskinesia. Results: NGS and a subsequent sequencing of the positive pathogenic or likely pathogenic variants, 5 patients (23%) were found to have a molecular defect. In particular, pathogenic variants were identified in <i>TEX11</i>, <i>CCDC39</i>, <i>CHD7</i>, and <i>NR5A1</i> genes. Moreover, 14 variants of unknown significance and 7 novel variants were found that require further functional studies and family segregation. Conclusion: This extended NGS-based diagnostic approach may represent a useful tool for the diagnosis of male infertility. The development of a custom-made gene panel by NGS seems capable of reducing the proportion of male idiopathic infertility.https://www.mdpi.com/2075-1729/10/10/242male infertilityNGS diagnosisdefects of primary spermatogenesishypogonadotropic hypogonadismprimary ciliary dyskinesia |
spellingShingle | Rossella Cannarella Vincenza Precone Giulia Guerri Gian Maria Busetto Gian Carlo Di Renzo Sandro Gerli Elena Manara Astrit Dautaj Matteo Bertelli Aldo Eugenio Calogero Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing Life male infertility NGS diagnosis defects of primary spermatogenesis hypogonadotropic hypogonadism primary ciliary dyskinesia |
title | Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing |
title_full | Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing |
title_fullStr | Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing |
title_full_unstemmed | Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing |
title_short | Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing |
title_sort | clinical evaluation of a custom gene panel as a tool for precision male infertility diagnosis by next generation sequencing |
topic | male infertility NGS diagnosis defects of primary spermatogenesis hypogonadotropic hypogonadism primary ciliary dyskinesia |
url | https://www.mdpi.com/2075-1729/10/10/242 |
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