Gene panel analysis of literature-based infertility genes in Sertoli cell-only syndrome patients
Sertoli cell-only syndrome (SCOS) is a condition of male infertility characterized by a total absence of spermatogenic cells in nearly all seminiferous tubules. Apart from well-established genetic changes such as Klinefelter syndrome, CFTR variants, and Y-chromosome microdeletions, several hundred...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
University of Sarajevo, Institute for Genetic Engineering and Biotechnology
2023-04-01
|
| Series: | Genetics & Applications |
| Subjects: | |
| Online Access: | https://genapp.ba/editions/index.php/journal/article/view/167 |
| _version_ | 1797839590361399296 |
|---|---|
| author | Monika Logara Klarić Lucija Žunić Tihana Marić Lovro Trgovec-Greif Filip Rokić Ana Merkler Robert Belužić Oliver Vugrek Ana Katušić Bojanac Maja Barbalić |
| author_facet | Monika Logara Klarić Lucija Žunić Tihana Marić Lovro Trgovec-Greif Filip Rokić Ana Merkler Robert Belužić Oliver Vugrek Ana Katušić Bojanac Maja Barbalić |
| author_sort | Monika Logara Klarić |
| collection | DOAJ |
| description |
Sertoli cell-only syndrome (SCOS) is a condition of male infertility characterized by a total absence of spermatogenic cells in nearly all seminiferous tubules. Apart from well-established genetic changes such as Klinefelter syndrome, CFTR variants, and Y-chromosome microdeletions, several hundred candidate genes were reported as associated with male infertility. We selected 92 evidence-based genes associated with infertility and investigated data from whole-exome sequencing in 6 individuals with clinically diagnosed SCOS. Eight heterozygous variants passed our filtering criteria, including population frequency ≤ 0.1% and high functional impact indicated by Sift, Polyphen, and CADD scores. Out of them, we considered only variants with putative autosomal dominant effects on infertility that were subsequently validated by Sanger sequencing. This filtering pipeline has led to the final likely causative variants detected in CHD7 and SCYP3 genes that potentially explain SCOS in two of our patients. Our discoveries suggest that gene panel testing of patients with SCOS could improve the diagnostic outcome; however, assembling a gene panel consisting of only genuine causative genes is crucial.
|
| first_indexed | 2024-04-09T16:00:27Z |
| format | Article |
| id | doaj.art-29d56289dc124944865532ae933c93de |
| institution | Directory Open Access Journal |
| issn | 2566-2937 2566-431X |
| language | English |
| last_indexed | 2024-04-09T16:00:27Z |
| publishDate | 2023-04-01 |
| publisher | University of Sarajevo, Institute for Genetic Engineering and Biotechnology |
| record_format | Article |
| series | Genetics & Applications |
| spelling | doaj.art-29d56289dc124944865532ae933c93de2023-04-25T11:32:16ZengUniversity of Sarajevo, Institute for Genetic Engineering and BiotechnologyGenetics & Applications2566-29372566-431X2023-04-017110.31383/ga.vol7iss1ga03Gene panel analysis of literature-based infertility genes in Sertoli cell-only syndrome patientsMonika Logara Klarić0Lucija Žunić1Tihana Marić2Lovro Trgovec-Greif3Filip Rokić4Ana Merkler5Robert Belužić6Oliver Vugrek7Ana Katušić Bojanac8Maja Barbalić9Genom Ltd, Zagreb, Croatia; Laboratory for Advanced Genomics, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, CroatiaGenom Ltd, Zagreb, CroatiaDepartment of Medical Biology, University of Zagreb, School of Medicine, Zagreb, Croatia; Center of Excellence in Reproductive and Regenerative Medicine, School of Medicine, Zagreb, CroatiaLaboratory for Advanced Genomics, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, CroatiaLaboratory for Advanced Genomics, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, CroatiaCenter of Excellence in Reproductive and Regenerative Medicine, School of Medicine, Zagreb, CroatiaDivision of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, CroatiaLaboratory for Advanced Genomics, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, CroatiaDepartment of Medical Biology, University of Zagreb, School of Medicine, Zagreb, Croatia; Center of Excellence in Reproductive and Regenerative Medicine, School of Medicine, Zagreb, CroatiaGenom Ltd, Zagreb, Croatia; Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia Sertoli cell-only syndrome (SCOS) is a condition of male infertility characterized by a total absence of spermatogenic cells in nearly all seminiferous tubules. Apart from well-established genetic changes such as Klinefelter syndrome, CFTR variants, and Y-chromosome microdeletions, several hundred candidate genes were reported as associated with male infertility. We selected 92 evidence-based genes associated with infertility and investigated data from whole-exome sequencing in 6 individuals with clinically diagnosed SCOS. Eight heterozygous variants passed our filtering criteria, including population frequency ≤ 0.1% and high functional impact indicated by Sift, Polyphen, and CADD scores. Out of them, we considered only variants with putative autosomal dominant effects on infertility that were subsequently validated by Sanger sequencing. This filtering pipeline has led to the final likely causative variants detected in CHD7 and SCYP3 genes that potentially explain SCOS in two of our patients. Our discoveries suggest that gene panel testing of patients with SCOS could improve the diagnostic outcome; however, assembling a gene panel consisting of only genuine causative genes is crucial. https://genapp.ba/editions/index.php/journal/article/view/167male infertilitySCOSWESpanel |
| spellingShingle | Monika Logara Klarić Lucija Žunić Tihana Marić Lovro Trgovec-Greif Filip Rokić Ana Merkler Robert Belužić Oliver Vugrek Ana Katušić Bojanac Maja Barbalić Gene panel analysis of literature-based infertility genes in Sertoli cell-only syndrome patients Genetics & Applications male infertility SCOS WES panel |
| title | Gene panel analysis of literature-based infertility genes in Sertoli cell-only syndrome patients |
| title_full | Gene panel analysis of literature-based infertility genes in Sertoli cell-only syndrome patients |
| title_fullStr | Gene panel analysis of literature-based infertility genes in Sertoli cell-only syndrome patients |
| title_full_unstemmed | Gene panel analysis of literature-based infertility genes in Sertoli cell-only syndrome patients |
| title_short | Gene panel analysis of literature-based infertility genes in Sertoli cell-only syndrome patients |
| title_sort | gene panel analysis of literature based infertility genes in sertoli cell only syndrome patients |
| topic | male infertility SCOS WES panel |
| url | https://genapp.ba/editions/index.php/journal/article/view/167 |
| work_keys_str_mv | AT monikalogaraklaric genepanelanalysisofliteraturebasedinfertilitygenesinsertolicellonlysyndromepatients AT lucijazunic genepanelanalysisofliteraturebasedinfertilitygenesinsertolicellonlysyndromepatients AT tihanamaric genepanelanalysisofliteraturebasedinfertilitygenesinsertolicellonlysyndromepatients AT lovrotrgovecgreif genepanelanalysisofliteraturebasedinfertilitygenesinsertolicellonlysyndromepatients AT filiprokic genepanelanalysisofliteraturebasedinfertilitygenesinsertolicellonlysyndromepatients AT anamerkler genepanelanalysisofliteraturebasedinfertilitygenesinsertolicellonlysyndromepatients AT robertbeluzic genepanelanalysisofliteraturebasedinfertilitygenesinsertolicellonlysyndromepatients AT olivervugrek genepanelanalysisofliteraturebasedinfertilitygenesinsertolicellonlysyndromepatients AT anakatusicbojanac genepanelanalysisofliteraturebasedinfertilitygenesinsertolicellonlysyndromepatients AT majabarbalic genepanelanalysisofliteraturebasedinfertilitygenesinsertolicellonlysyndromepatients |