Analysis of 29 Targeted Genes for Non-Obstructive Azoospermia: The Relationship between Genetic Testing and Testicular Histology
Purpose: To analyze the presence of potentially pathogenic variants of 29 candidate genes known to cause spermatogenic failure (SPGF) in patients with non-obstructive azoospermia (NOA) who underwent testicular histology. Materials and Methods: Forty-eight patients with unexplained NOA referred to...
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| Format: | Article |
| Language: | English |
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Korean Society for Sexual Medicine and Andrology
2023-04-01
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| Series: | The World Journal of Men's Health |
| Subjects: |
| _version_ | 1827987671257972736 |
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| author | Rossella Cannarella Matteo Bertelli Rosita A. Condorelli Marija Vilaj Sandro La Vignera Davor Jezek Aldo E. Calogero |
| author_facet | Rossella Cannarella Matteo Bertelli Rosita A. Condorelli Marija Vilaj Sandro La Vignera Davor Jezek Aldo E. Calogero |
| author_sort | Rossella Cannarella |
| collection | DOAJ |
| description | Purpose: To analyze the presence of potentially pathogenic variants of 29 candidate genes known to cause spermatogenic
failure (SPGF) in patients with non-obstructive azoospermia (NOA) who underwent testicular histology.
Materials and Methods: Forty-eight patients with unexplained NOA referred to the Department of Transfusion Medicine and
Transplantation Biology, University Hospital Center Zagreb, Zagreb, Croatia for testicular biopsy. They were divided into
three groups: those who had cryptorchidism (n=9), those with varicocele (n=14), and those with idiopathic NOA (n=25). All
included patients underwent blood withdrawal for next-generation sequencing (NGS) analysis and gene sequencing.
Results: We found a possible genetic cause in 4 patients with idiopathic NOA (16%) and in 2 with cryptorchidism (22%). No
pathogenic or possibly pathogenic mutations were identified in patients with varicocele. Variants of undetermined significance
(VUS) were found in 11 patients with idiopathic NOA (44%), 3 with cryptorchidism (33%), and 8 patients with varicocele
(57%). VUSs of the USP9Y gene were the most frequently as they were found in 14 out of 48 patients (29%). In particular,
the VUS USP9Y c.7434+14del was found in 11 patients. They showed varied histological pictures, including Sertoli cellonly
syndrome, mixed atrophy, and hypospermatogenesis, regardless of cryptorchidism or varicocele. No direct correlation
was found between the gene mutation/variant and the testicular histological picture.
Conclusions: Different mutations of the same gene cause various testicular histological pictures. These results suggest that
it is not the gene itself but the type of mutation/variation that determines the testicular histology picture. Based on the data
presented above, it remains challenging to design a genetic panel with prognostic value for the outcome of testicular sperm
extraction in patients with NOA. |
| first_indexed | 2024-04-09T23:51:44Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2287-4208 2287-4690 |
| language | English |
| last_indexed | 2024-04-09T23:51:44Z |
| publishDate | 2023-04-01 |
| publisher | Korean Society for Sexual Medicine and Andrology |
| record_format | Article |
| series | The World Journal of Men's Health |
| spelling | doaj.art-b4200db9367f4127bf8c883ff31f46662023-03-17T07:22:22ZengKorean Society for Sexual Medicine and AndrologyThe World Journal of Men's Health2287-42082287-46902023-04-0141242243310.5534/wjmh.220009Analysis of 29 Targeted Genes for Non-Obstructive Azoospermia: The Relationship between Genetic Testing and Testicular HistologyRossella Cannarella0https://orcid.org/0000-0003-4599-8487Matteo Bertelli1https://orcid.org/0000-0002-9552-221XRosita A. Condorelli2https://orcid.org/0000-0002-5217-9343Marija Vilaj3https://orcid.org/0000-0003-3877-467XSandro La Vignera4https://orcid.org/0000-0002-7113-2372Davor Jezek5https://orcid.org/0000-0002-1528-5462Aldo E. Calogero6https://orcid.org/0000-0001-6950-335XDepartment of Clinical and Experimental Medicine, University of Catania, CataniaMAGI Euregio, Bolzano, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, CataniaDepartment of Transfusion Medicine and Transplantation Biology, University Hospital Center ZagrebDepartment of Clinical and Experimental Medicine, University of Catania, CataniaDepartment of Transfusion Medicine and Transplantation Biology, University Hospital Center ZagrebDepartment of Clinical and Experimental Medicine, University of Catania, CataniaPurpose: To analyze the presence of potentially pathogenic variants of 29 candidate genes known to cause spermatogenic failure (SPGF) in patients with non-obstructive azoospermia (NOA) who underwent testicular histology. Materials and Methods: Forty-eight patients with unexplained NOA referred to the Department of Transfusion Medicine and Transplantation Biology, University Hospital Center Zagreb, Zagreb, Croatia for testicular biopsy. They were divided into three groups: those who had cryptorchidism (n=9), those with varicocele (n=14), and those with idiopathic NOA (n=25). All included patients underwent blood withdrawal for next-generation sequencing (NGS) analysis and gene sequencing. Results: We found a possible genetic cause in 4 patients with idiopathic NOA (16%) and in 2 with cryptorchidism (22%). No pathogenic or possibly pathogenic mutations were identified in patients with varicocele. Variants of undetermined significance (VUS) were found in 11 patients with idiopathic NOA (44%), 3 with cryptorchidism (33%), and 8 patients with varicocele (57%). VUSs of the USP9Y gene were the most frequently as they were found in 14 out of 48 patients (29%). In particular, the VUS USP9Y c.7434+14del was found in 11 patients. They showed varied histological pictures, including Sertoli cellonly syndrome, mixed atrophy, and hypospermatogenesis, regardless of cryptorchidism or varicocele. No direct correlation was found between the gene mutation/variant and the testicular histological picture. Conclusions: Different mutations of the same gene cause various testicular histological pictures. These results suggest that it is not the gene itself but the type of mutation/variation that determines the testicular histology picture. Based on the data presented above, it remains challenging to design a genetic panel with prognostic value for the outcome of testicular sperm extraction in patients with NOA.azoospermiamale infertilitynext-generation sequencingspermatogenesistesticular histology |
| spellingShingle | Rossella Cannarella Matteo Bertelli Rosita A. Condorelli Marija Vilaj Sandro La Vignera Davor Jezek Aldo E. Calogero Analysis of 29 Targeted Genes for Non-Obstructive Azoospermia: The Relationship between Genetic Testing and Testicular Histology The World Journal of Men's Health azoospermia male infertility next-generation sequencing spermatogenesis testicular histology |
| title | Analysis of 29 Targeted Genes for Non-Obstructive Azoospermia: The Relationship between Genetic Testing and Testicular Histology |
| title_full | Analysis of 29 Targeted Genes for Non-Obstructive Azoospermia: The Relationship between Genetic Testing and Testicular Histology |
| title_fullStr | Analysis of 29 Targeted Genes for Non-Obstructive Azoospermia: The Relationship between Genetic Testing and Testicular Histology |
| title_full_unstemmed | Analysis of 29 Targeted Genes for Non-Obstructive Azoospermia: The Relationship between Genetic Testing and Testicular Histology |
| title_short | Analysis of 29 Targeted Genes for Non-Obstructive Azoospermia: The Relationship between Genetic Testing and Testicular Histology |
| title_sort | analysis of 29 targeted genes for non obstructive azoospermia the relationship between genetic testing and testicular histology |
| topic | azoospermia male infertility next-generation sequencing spermatogenesis testicular histology |
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