Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made Panel
BackgroundInfertility affects about 7% of the general male population. The underlying cause of male infertility is undefined in about 50% of cases (idiopathic infertility). The number of genes involved in human spermatogenesis is over two thousand. Therefore, it is essential to analyze a large numbe...
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doaj-7625043ece0147cb857e108bb71f840b2021-01-26T16:35:39ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-01-011110.3389/fendo.2020.605237605237Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made PanelVincenza Precone0Rossella Cannarella1Stefano Paolacci2Gian Maria Busetto3Tommaso Beccari4Liborio Stuppia5Gerolamo Tonini6Alessandra Zulian7Giuseppe Marceddu8Aldo E. Calogero9Matteo Bertelli10Matteo Bertelli11Matteo Bertelli12MAGI EUREGIO, Bolzano, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, Catania, ItalyMAGI’S LAB, Rovereto, ItalyDepartment of Urology, “Sapienza” University of Rome, Policlinico Umberto I, Rome, ItalyDepartment of Pharmaceutical Sciences, University of Perugia, Perugia, ItalyDepartment of Psychological, Health and Territorial Sciences, School of Medicine and Health Sciences, “G. d’Annunzio” University of Chieti-Pescara, Chieti, ItalyDepartment of Surgery, Fondazione Poliambulanza, Brescia, ItalyMAGI’S LAB, Rovereto, ItalyMAGI EUREGIO, Bolzano, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, Catania, ItalyMAGI EUREGIO, Bolzano, ItalyMAGI’S LAB, Rovereto, ItalyEBTNA-LAB, Rovereto, ItalyBackgroundInfertility affects about 7% of the general male population. The underlying cause of male infertility is undefined in about 50% of cases (idiopathic infertility). The number of genes involved in human spermatogenesis is over two thousand. Therefore, it is essential to analyze a large number of genes that may be involved in male infertility. This study aimed to test idiopathic male infertile patients negative for a validated panel of “diagnostic” genes, for a wide panel of genes that we have defined as “pre-diagnostic.”MethodsWe developed a next-generation sequencing (NGS) gene panel including 65 pre-diagnostic genes that were used in 12 patients who were negative to a diagnostic genetic test for male infertility disorders, including primary spermatogenic failure and central hypogonadism, consisting of 110 genes.ResultsAfter NGS sequencing, variants in pre-diagnostic genes were identified in 10/12 patients who were negative to a diagnostic test for primary spermatogenic failure (n = 9) or central hypogonadism (n = 1) due to mutations of single genes. Two pathogenic variants of DNAH5 and CFTR genes and three uncertain significance variants of DNAI1, DNAH11, and CCDC40 genes were found. Moreover, three variants with high impact were found in AMELY, CATSPER 2, and ADCY10 genes.ConclusionThis study suggests that searching for pre-diagnostic genes may be of relevance to find the cause of infertility in patients with apparently idiopathic primary spermatogenic failure due to mutations of single genes and central hypogonadism.https://www.frontiersin.org/articles/10.3389/fendo.2020.605237/fullmale infertilitynext-generation sequencinggenetic testspermatogenesis defectsazoospermiaoligozoospermia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Vincenza Precone Rossella Cannarella Stefano Paolacci Gian Maria Busetto Tommaso Beccari Liborio Stuppia Gerolamo Tonini Alessandra Zulian Giuseppe Marceddu Aldo E. Calogero Matteo Bertelli Matteo Bertelli Matteo Bertelli |
spellingShingle |
Vincenza Precone Rossella Cannarella Stefano Paolacci Gian Maria Busetto Tommaso Beccari Liborio Stuppia Gerolamo Tonini Alessandra Zulian Giuseppe Marceddu Aldo E. Calogero Matteo Bertelli Matteo Bertelli Matteo Bertelli Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made Panel Frontiers in Endocrinology male infertility next-generation sequencing genetic test spermatogenesis defects azoospermia oligozoospermia |
author_facet |
Vincenza Precone Rossella Cannarella Stefano Paolacci Gian Maria Busetto Tommaso Beccari Liborio Stuppia Gerolamo Tonini Alessandra Zulian Giuseppe Marceddu Aldo E. Calogero Matteo Bertelli Matteo Bertelli Matteo Bertelli |
author_sort |
Vincenza Precone |
title |
Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made Panel |
title_short |
Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made Panel |
title_full |
Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made Panel |
title_fullStr |
Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made Panel |
title_full_unstemmed |
Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made Panel |
title_sort |
male infertility diagnosis: improvement of genetic analysis performance by the introduction of pre-diagnostic genes in a next-generation sequencing custom-made panel |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2021-01-01 |
description |
BackgroundInfertility affects about 7% of the general male population. The underlying cause of male infertility is undefined in about 50% of cases (idiopathic infertility). The number of genes involved in human spermatogenesis is over two thousand. Therefore, it is essential to analyze a large number of genes that may be involved in male infertility. This study aimed to test idiopathic male infertile patients negative for a validated panel of “diagnostic” genes, for a wide panel of genes that we have defined as “pre-diagnostic.”MethodsWe developed a next-generation sequencing (NGS) gene panel including 65 pre-diagnostic genes that were used in 12 patients who were negative to a diagnostic genetic test for male infertility disorders, including primary spermatogenic failure and central hypogonadism, consisting of 110 genes.ResultsAfter NGS sequencing, variants in pre-diagnostic genes were identified in 10/12 patients who were negative to a diagnostic test for primary spermatogenic failure (n = 9) or central hypogonadism (n = 1) due to mutations of single genes. Two pathogenic variants of DNAH5 and CFTR genes and three uncertain significance variants of DNAI1, DNAH11, and CCDC40 genes were found. Moreover, three variants with high impact were found in AMELY, CATSPER 2, and ADCY10 genes.ConclusionThis study suggests that searching for pre-diagnostic genes may be of relevance to find the cause of infertility in patients with apparently idiopathic primary spermatogenic failure due to mutations of single genes and central hypogonadism. |
topic |
male infertility next-generation sequencing genetic test spermatogenesis defects azoospermia oligozoospermia |
url |
https://www.frontiersin.org/articles/10.3389/fendo.2020.605237/full |
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