Non-obstrüktif azospermik (NOA) infertil hastalarda yeni nesil dizi analizi (NGS) ile genetik etiyolojinin araştırılması
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Dosyalar
Tarih
2022
Yazarlar
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Yayıncı
Trakya Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Dünya çapındaki çiftlerin yaklaşık %10-15’inde görülmekte olan infertilite, klinikte 12 ay veya daha uzun süreli düzenli korunmasız cinsel ilişki durumundan sonra gebelik elde edilememesi olarak tanımlanan hem kadınlarda hem de erkeklerde görülen bir üreme sistemi hastalığıdır. Azospermi, semende spermin yokluğu durumudur. Non-obstrüktif azospermi (NOA) ise erkek infertilitesinin en şiddetli formudur. Spermatogenezde oluşabilecek hatalardan (pretestiküler ve testiküler) kaynaklanmaktadır. Çalışmamıza Trakya Üniversitesi Tıbbi Genetik Anabilim Dalı Genetik Hastalıklar Değerlendirme Merkezine non-obstrüktif azospermi öyküsü ile yönlendirilen, sayısal ve yapısal kromozom anomalisi ve Y kromozomunda mikrodelesyon saptanmayan 40 erkek hasta dahil edilmiştir. 21 geni (TERB1, MAJIN, MTRR, PIWIL1, SOX10, SIRPG, SIRPA, DNAH6, MEI1, DNAH17, ZMYND15, DNAH1, DPY19L2, SEPTIN12, KLHL10, DDX25, LHB, CATSPER1, NPHP4, CFTR ve FKBPL) içinde barındıran özgün tasarlanmış çoklu gen paneli kullanılarak yeni nesil dizi analizi (NGS) teknolojisiyle non-obstrüktif azosperminin genetik etiyolojinin araştırılmıştır. Çalışmamızda 40 hastanın 17‘sinde (%42,5) 13 farklı gende 24 varyant saptandı. ACMG-2015 kriterlerine göre 6’sı patojenik, 5’i olası patojenik ve 18’i klinik önemi belirsiz (VUS) varyant saptandı. 2 gende (DPY19L2 ve KLHL10) yeni varyant saptandı. Dünya çapında üreme sistemi hastalıklarında önemli bir artış gözlenmektedir. İnfertilite bu hastalıklardan bir tanesidir. Non-obstrüktif azospermi ise erkek infertilitesinin en şiddetli formudur. Genetik ve klinik olarak heterojen bir endikasyondur. Bundan dolayı non-obstrüktif azospermi tanısı almış infertil hastalarda özgün tasarlanmış çoklu gen panellerinin yeni nesil dizilenmesi tanı süreçlerine yardımcı olabileceği ve genetik danışmanlık da dahil olmak üzere hastalara uygun danışmanlık ve tedavinin sağlanması açısından kritik öneme sahip olabileceği öngörüsündeyiz.
Infertility, which is seen in approximately 10-15% of couples worldwide, is a reproduc- tive system disease seen in both women and men, which is clinically defined as the inability to achieve pregnancy after 12 months or more of regular unprotected sexual intercourse. Azoospermia is the absence of sperm in the semen. Non-obstructive azoospermia (NOA) is the most severe form of male infertility. It is caused by errors that may occur in spermatogenesis (pretesticular and testicular). Forty male patients who were referred to Trakya University, Department of Medical Genetics, Genetic Diseases Evaluation Center with a history of non-obstructive azoospermia, who had no numerical and structural chromosomal anomaly and no microdeletion in the Y chromosome were included in our study. The genetic etiology of non-obstructive azoospermia was investigated with next-generation sequencing (NGS) technology, using a custom designed multi-gene panel containing 21 genes (TERB1, MAJIN, MTRR, PIWIL1, SOX10, SIRPG, SIRPA, DNAH6, MEI1, DNAH17, ZMYND15, DNAH1, DPY19L2, SEPTIN12, KLHL10, DDX25, LHB, CATSPER1, NPHP4, CFTR and FKBPL). In our study, 24 variants in 13 different genes were detected in 17 (42.5%) of 40 patients. According to the ACMG-2015 criteria, 6 pathogenic variants, 5 probable pathogenic variants and 18 variant of uncertain significance (VUS) variants were detected. A novel variant was detected in 2 genes (DPY19L2 and KLHL10). There is a significant increase in reproductive system diseases worldwide. Infertility is one of these diseases. Non-obstructive azoospermia is the most severe form of male infertility. It is a genetically and clinically heterogeneous indication. Therefore, we predict that next-generation sequencing of custom designed multi-gene panels in infertile patients diagnosed with non-obstructive azoospermia may help the diagnostic processes and be of critical importance in terms of providing appropriate counseling and treatment, including genetic counseling.
Infertility, which is seen in approximately 10-15% of couples worldwide, is a reproduc- tive system disease seen in both women and men, which is clinically defined as the inability to achieve pregnancy after 12 months or more of regular unprotected sexual intercourse. Azoospermia is the absence of sperm in the semen. Non-obstructive azoospermia (NOA) is the most severe form of male infertility. It is caused by errors that may occur in spermatogenesis (pretesticular and testicular). Forty male patients who were referred to Trakya University, Department of Medical Genetics, Genetic Diseases Evaluation Center with a history of non-obstructive azoospermia, who had no numerical and structural chromosomal anomaly and no microdeletion in the Y chromosome were included in our study. The genetic etiology of non-obstructive azoospermia was investigated with next-generation sequencing (NGS) technology, using a custom designed multi-gene panel containing 21 genes (TERB1, MAJIN, MTRR, PIWIL1, SOX10, SIRPG, SIRPA, DNAH6, MEI1, DNAH17, ZMYND15, DNAH1, DPY19L2, SEPTIN12, KLHL10, DDX25, LHB, CATSPER1, NPHP4, CFTR and FKBPL). In our study, 24 variants in 13 different genes were detected in 17 (42.5%) of 40 patients. According to the ACMG-2015 criteria, 6 pathogenic variants, 5 probable pathogenic variants and 18 variant of uncertain significance (VUS) variants were detected. A novel variant was detected in 2 genes (DPY19L2 and KLHL10). There is a significant increase in reproductive system diseases worldwide. Infertility is one of these diseases. Non-obstructive azoospermia is the most severe form of male infertility. It is a genetically and clinically heterogeneous indication. Therefore, we predict that next-generation sequencing of custom designed multi-gene panels in infertile patients diagnosed with non-obstructive azoospermia may help the diagnostic processes and be of critical importance in terms of providing appropriate counseling and treatment, including genetic counseling.
Açıklama
Anahtar Kelimeler
İnfertilite, Azospermi, Non-obstrüktif azospermi (NOA), Yeni nesil dizi analizi (NGS), Infertility, Azoospermia, Non-obstructive azoospermia (NOA), Next gene- ration sequencing (NGS)
