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Мужское бесплодие: взгляд генетика на актуальную проблему
Мужское бесплодие: взгляд генетика на актуальную проблему
Черных В.Б., Соловова О.А. Мужское бесплодие: взгляд генетика на актуальную проблему. Consilium Medicum. 2019; 21 (7): 19–24. DOI: 10.26442/20751753.2019.7.190517
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Аннотация
В последние годы вклад «мужского фактора» в проблемы репродукции человека значительно возрос. Это связано как со снижением показателей семенной жидкости и мужской фертильности, так и ростом знаний в области андрологии, репродуктивной медицины и генетики. Нарушение фертильности у мужчин может быть вызвано различными причинами и связано с генетическими, средовыми факторами или их сочетанием, проявляться разными клиническими заболеваниями или состояниями и часто связано с изменением сперматологических показателей. Наличие или отсутствие синдромальной формы мужского бесплодия, форма патозооспермии в значительной мере определяют стратегию генетического обследования пациента. В диагностику причин мужского бесплодия, связанного с азооспермией и олигозооспермией тяжелой степени, широко вошли стандартное цитогенетическое исследование (анализ кариотипа), анализ микроделеций Y-хромосомы в локусе AZF, а также вариантов гена CFTR. Хромосомные аномалии, структурные аномалии и вариации числа копий аутосом и половых хромосом, генные мутации/варианты и эпигенетические нарушения, анеуплоидия в сперматозоидах могут оказывать негативное воздействие на мужскую фертильность, приводя к нарушению формирования пола, нарушению развития органов половой системы, сперматогенеза, мейоза, снижая фертильностные параметры сперматозоидов. Выраженная гетерогенность генетических причин многих форм патозооспермии и относительная редкость синдромальных нарушений репродуктивной системы и мужского бесплодия существенно затрудняют диагностику, и поэтому пациентам с нарушением репродукции неясного генеза, генетической или предположительно генетической этиологии необходимо комплексное обследование с использованием геномных и метагеномных технологий. Медико-генетическое обследование и консультирование должны проводиться не на поздних этапах обследования пациентов с бесплодием, как «исключающие генетический фактор», а быть неотъемлемой частью комплексного клинического обследования пациентов и супружеских пар с нарушением репродукции.
Ключевые слова: мужское бесплодие, азооспермия, олигозооспермия, астено-/тератозооспермия, хромосомные аномалии, половые хромосомы, микроделеции, вариации числа копий, генные варианты, AZF, CFTR.
Ключевые слова: мужское бесплодие, азооспермия, олигозооспермия, астено-/тератозооспермия, хромосомные аномалии, половые хромосомы, микроделеции, вариации числа копий, генные варианты, AZF, CFTR.
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In recent years, a contribution of the “male factor” to problems of human reproduction has increased significantly. This is due to a decrease in parameters of seminal fluid and male fertility, as well as an increase in knowledge in the field of andrology, reproductive medicine and genetics. Impaired fertility in men can be caused by various reasons and is associated with genetic and environmental factors or a combination thereof. It manifests itself in different clinical diseases or conditions and is often due to a change in spermatological parameters. The presence or absence of syndromic male infertility, a type of pathozoospermia, largely determine a strategy for genetic examination of the patient. Diagnosis of male infertility which is associated with severe azoospermia and severe oligozoospermia includes a standard cytogenetic analysis (karyotyping), analysis of Y chromosome microdeletions at the AZF region, and CFTR gene variants. Chromosomal abnormalities, structural anomalies and variations in the copy number of autosomes and sex chromosomes, gene mutations / variants and epigenetic abnormalities, aneuploidy in spermatozoa can have a negative effect on male fertility, leading to impaired sex formation, impaired development of the reproductive system, impaired spermatogenesis and meiosis and to a decrease in fertility parameters of sperm. Heterogeneity of genetic causes of many forms of pathozoospermia and a relative rarity of syndromic disorders of the reproductive system and male infertility significantly complicate diagnosis, and therefore, patients with impaired fertility of unknown origin, genetic or presumably genetic etiology, need a comprehensive examination using genomic and metagenomic technologies. Genetic testing and counseling of patients with infertility should not be carried out at late stages of examination as “exclusion of the genetic factor”, but they should be an integral part of a comprehensive clinical examination of patients and couples with impaired reproduction.
Key words: male infertility, azoospermia, oligozoospermia, astheno- / teratozoospermia, chromosomal abnormalities, sex chromosomes, microdeletions, copy number variations, gene variants, AZF, CFTR.
Key words: male infertility, azoospermia, oligozoospermia, astheno- / teratozoospermia, chromosomal abnormalities, sex chromosomes, microdeletions, copy number variations, gene variants, AZF, CFTR.
Полный текст
Список литературы
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[Chernykh V.B., Stepanova A.A., Beskorovainaia T.S. et al. The frequency and spectrum of mutations and the IVS8-T polymorphism of the CFTR gene in Russian infertile men. Genetika. 2010; 46 (6): 844–52 (in Russian).]
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[Repina S.A., Krasovskii S.A., Rozhivanov R.V. et al. Andrology examination of patients with pancreatic-sufficient and pancreatic-insufficient Cystic Fibrosis. Andrology and Genital Surgery. 2018; 19 (2): 31–9 (in Russian).]
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[Bragina E.E., Sorokina T.M., Arifulin E.A., Kurilo L.F. Genetically determined patozoospermia. Literature review and research results. Andrology and Genital Surgery. 2015; 16 (3): 29–39 (in Russian).]
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[Chernykh V.B. Cystic Fibrosis gene and male infertility. Andrology and Genital Surgery. 2010; 4: 23–31 (in Russian).]
2. Krausz C, Riera-Escamilla A. Genetics of male infertility. Nat Rev Urol 2018; 15: 369–84.
3. Руководство ВОЗ по исследованию и обработке эякулята человека. Пер. с англ. Н.П.Макарова, науч. ред. Л.Ф.Курило. 5-е изд. М.: Капитал Принт, 2012.
[WHO guidelines for the study and treatment of human ejaculate. Transl. from English N.P. Makarova, scientific ed. L.F. Kurilo. 5th ed. Moscow: Capital Print, 2012 (in Russian).]
4. Андреева М.В., Хаят С.Ш., Сорокина Т.М. и др. Формы патозооспермии у мужчин с бесплодием в браке и/или с нарушениями репродуктивной системы. Андрология и генитальная хирургия. 2017; 18 (2): 33–8.
[Andreeva M.V., Khaiat S.Sh., Sorokina T.M. et al. Types of pathozoospermia in men with infertility in marriage аnd/or disorders of reproductive system. Andrology and Genital Surgery. 2017; 18 (2): 33–8 (in Russian).]
5. Черных В.Б., Яманди Т.А., Сафина Н.Ю. Новые молекулярные технологии в диагностике генетических причин мужского бесплодия. Андрология и генитальная хирургия. 2017; 18 (1): 10–22.
[Chernykh V.B., Iamandi T.A., Safina N.Iu. New molecular technologies in genetic diagnosis of male infertility. Andrology and Genital Surgery. 2017; 18 (1): 10–22 (in Russian).]
6. Tuttelmann F, Simoni M et al. Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome. PLOS One 2011; 6 (4): e19426.
7. Соловова О.А., Черных В.Б. Гены несиндромальных форм азооспермии и олигозооспермии тяжелой степени. Андрология и генитальная хирургия. 2019; 20 (2): 16–28.
[Solovova O.A., Chernykh V.B. Genetic causes of nonsyndromic forms of azoospermia and severe oligozoospermia in infertility men. Andrology and Genital Surgery. 2019; 20 (2): 16–28 (in Russian).]
8. Сафина Н.Ю., Яманди Т.А., Черных В.Б. и др. Генетические факторы мужского бесплодия, их сочетания и спермиологическая характеристика мужчин с нарушением фертильности. Андрология и генитальная хирургия. 2018; 19 (2): 40–51.
[Safina N.Iu., Iamandi T.A., Chernykh V.B. et al. Genetic factors of male infertility, their combinations and the spermatological characteristics of men with fertility failures. Andrology and Genital Surgery. 2018; 19 (2): 40–51 (in Russian).]
9. Olszewska M, Barciszewska MZ, Fraczek M et al. Global methylation status of sperm DNA in carriers of chromosome structural aberrations. Asian J Androl 2017; 19 (1): 117–24.
10. McKinlay Gardner RJ, Amor DJ. Gardner and Sutherland’s Chromosome Abnormalities and Genetic Counseling (5 ed.). Oxford University Press, 2018.
11. Черных В.Б. Гоносомные аномалии и CNV, и их диагностика. Мед. генетика. 2018; 17 (10): 8–14.
[Chernykh V.B. Sex chromosomes abnormalities and CNVs, and their diagnosis. Medical Genetics. 2018; 17 (10): 8–14 (in Russian).]
12. Bonomi M, Rochira V, Pasquali D et al. Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Invest 2017; 40: 123–34.
13. Vorona E, Zitzmann M, Gromoll J et al. Clinical, endocrinological, and epigenetic features of the 46,XX male syndrome, compared with 47,XXY Klinefelter patients. J Clin Endocrinol Metab 2007; 92: 3458–65.
14. Wong EC, Ferguson KA, Chow V, Ma S. Sperm aneuploidy and meiotic sex chromosome configurations in an infertile XYY male. Hum Reprod 2007; 23 (2): 374–8.
15. Maione L, Dwyer AA, Francou B et al. Genetics in endocrinology: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing. Eur J Endocrinol 2018; 178 (3): R55–R80.
16. Alkelai A, Olender T, Dode C et al. Next-generation sequencing of patients with congenital anosmia. Eur J Hum Genet 2017; 25 (12): 1377–87.
17. Boehm U, Bouloux PM, Dattani MT et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism – pathogenesis, diagnosis and treatment. Nat Rev Endocrin 2015; 11: 547–64.
18. Черных В.Б., Руднева С.А., Сорокина Т.М. и др. Характеристика состояния сперматогенеза у мужчин с бесплодием, имеющих различные типы делеций AZFc-региона. Андрология и генитальная хирургия. 2014; 15 (2): 48–57.
[Chernykh V.B., Rudneva S.A., Sorokina T.M. et al. Characteristics of spermatogenesis in infertile men with the AZFc region deletions. Andrology and Genital Surgery. 2014; 15 (2): 48–57 (in Russian).]
19. Черных В.Б. AZF делеции – частая генетическая причина бесплодия у мужчин: современное состояние исследований. Проблемы репродукции. 2009; 15 (1): 10–5.
[Chernykh V.B. AZF deletions are common genetic cause of male infertility: current state of research. Problemy reproduktsii. 2009; 15 (1): 10–5 (in Russian).]
20. Черных В.Б., Степанова А.А., Бескоровайная Т.С. и др. Частота и спектр мутаций и IVS8T-полиморфизма гена CFTR среди российских мужчин с бесплодием. Генетика. 2010; 46 (6): 844–52.
[Chernykh V.B., Stepanova A.A., Beskorovainaia T.S. et al. The frequency and spectrum of mutations and the IVS8-T polymorphism of the CFTR gene in Russian infertile men. Genetika. 2010; 46 (6): 844–52 (in Russian).]
21. Репина С.А., Красовский С.А., Роживанов Р.В. и др. Андрологическое обследование пациентов с легочной и смешанной формами муковисцидоза. Андрология и генитальная хирургия. 2018; 19 (2): 31–9.
[Repina S.A., Krasovskii S.A., Rozhivanov R.V. et al. Andrology examination of patients with pancreatic-sufficient and pancreatic-insufficient Cystic Fibrosis. Andrology and Genital Surgery. 2018; 19 (2): 31–9 (in Russian).]
22. Штаут М.И., Сорокина Т.М., Курило Л.Ф. и др. Сравнительный анализ результатов спермиологического исследования у пациентов с азооспермией, вызванной муковисцидозом и синдромом врожденной двусторонней аплазии семявыносящих протоков. Андрология и генитальная хирургия. 2019; 20 (1): 82–90.
[Shtaut M.I., Sorokina T.M., Kurilo L.F. et al. Comparative analysis of the results semen examination in patients with azoospermia caused by cystic fibrosis and congenital bilateral aplasia of vas deferens syndrome. Andrology and Genital Surgery. 2019; 20 (1): 82–90 (in Russian).]
23. Репина С.А., Красовский С.А., Шмарина Г.В. и др. Состояние репродуктивной системы и алгоритм решения вопроса деторождения у мужчин с муковисцидозом. Альманах клинической медицины. 2019; 47 (1): 26–37.
[Repina S.A., Krasovskii S.A., Shmarina G.V. et al. Reproductive system status and the algorithm to solve fertility issues in men with cystic fibrosis. Almanac of Clinical Medicine. 2019; 47 (1): 26–37 (in Russian).]
24. Брагина Е.Е., Сорокина Т.М., Арифулин Е.А., Курило Л.Ф. Генетически обусловленные формы патозооспермии. Обзор литературы и результаты исследований. Андрология и генитальная хирургия. 2015; 16 (3): 29–39.
[Bragina E.E., Sorokina T.M., Arifulin E.A., Kurilo L.F. Genetically determined patozoospermia. Literature review and research results. Andrology and Genital Surgery. 2015; 16 (3): 29–39 (in Russian).]
25. Coutton C, Escoffier J, Martinez G et al. Teratozoospermia: spotlight on the main genetic actors in the human. Hum Reprod Update 2015; 21 (4): 455–85.
26. De Braekeleer M, Nguyen MH, Morel F, Perrin A. Genetic aspects of monomorphic teratozoospermia: a review. J Assist Reprod Genet 2015; 32 (4): 615–23.
27. Ben Khelifa M, Zouari R, Harbuz R et al. A new AURKC mutation causing macrozoospermia: implications for human spermatogenesis and clinical diagnosis. Mol Hum Reprod 2011; 17 (12): 762–8.
28. Ghédir H, Braham A, Viville S et al. Comparison of sperm morphology and nuclear sperm quality in SPATA16‐ and DPY19L2‐mutated globozoospermic patients. Andrologia 2019; 51 (6): e13277.
29. Tang S, Wang X, Li W et al. Biallelic mutations in CFAP43 and CFAP44 cause male infertility with multiple morphological abnormalities of the sperm flagella. Am J Hum Genet 2017; 100 (6): 854–64.
30. Черных В.Б. Ген муковисцидоза и нарушение фертильности у мужчин. Андрология и генитальная хирургия. 2010; 4: 23–31.
[Chernykh V.B. Cystic Fibrosis gene and male infertility. Andrology and Genital Surgery. 2010; 4: 23–31 (in Russian).]
________________________________________________
1. Skakkebaek NE, Rajpert-De Meyts E, Buck Louis GM et al. Male reproductive disorders and fertility trends: Influences of environment and genetic susceptibility. Physiol Rev 2016; 96 (1): 55–97.
2. Krausz C, Riera-Escamilla A. Genetics of male infertility. Nat Rev Urol 2018; 15: 369–84.
3. WHO guidelines for the study and treatment of human ejaculate. Transl. from English N.P. Makarova, scientific ed. L.F. Kurilo. 5th ed. Moscow: Capital Print, 2012 (in Russian).
4. Andreeva M.V., Khaiat S.Sh., Sorokina T.M. et al. Types of pathozoospermia in men with infertility in marriage аnd/or disorders of reproductive system. Andrology and Genital Surgery. 2017; 18 (2): 33–8 (in Russian).
5. Chernykh V.B., Iamandi T.A., Safina N.Iu. New molecular technologies in genetic diagnosis of male infertility. Andrology and Genital Surgery. 2017; 18 (1): 10–22 (in Russian).
6. Tuttelmann F, Simoni M et al. Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome. PLOS One 2011; 6 (4): e19426.
7. Solovova O.A., Chernykh V.B. Genetic causes of nonsyndromic forms of azoospermia and severe oligozoospermia in infertility men. Andrology and Genital Surgery. 2019; 20 (2): 16–28 (in Russian).
8. Safina N.Iu., Iamandi T.A., Chernykh V.B. et al. Genetic factors of male infertility, their combinations and the spermatological characteristics of men with fertility failures. Andrology and Genital Surgery. 2018; 19 (2): 40–51 (in Russian).
9. Olszewska M, Barciszewska MZ, Fraczek M et al. Global methylation status of sperm DNA in carriers of chromosome structural aberrations. Asian J Androl 2017; 19 (1): 117–24.
10. McKinlay Gardner RJ, Amor DJ. Gardner and Sutherland’s Chromosome Abnormalities and Genetic Counseling (5 ed.). Oxford University Press, 2018.
11. Chernykh V.B. Sex chromosomes abnormalities and CNVs, and their diagnosis. Medical Genetics. 2018; 17 (10): 8–14 (in Russian).
12. Bonomi M, Rochira V, Pasquali D et al. Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Invest 2017; 40: 123–34.
13. Vorona E, Zitzmann M, Gromoll J et al. Clinical, endocrinological, and epigenetic features of the 46,XX male syndrome, compared with 47,XXY Klinefelter patients. J Clin Endocrinol Metab 2007; 92: 3458–65.
14. Wong EC, Ferguson KA, Chow V, Ma S. Sperm aneuploidy and meiotic sex chromosome configurations in an infertile XYY male. Hum Reprod 2007; 23 (2): 374–8.
15. Maione L, Dwyer AA, Francou B et al. Genetics in endocrinology: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing. Eur J Endocrinol 2018; 178 (3): R55–R80.
16. Alkelai A, Olender T, Dode C et al. Next-generation sequencing of patients with congenital anosmia. Eur J Hum Genet 2017; 25 (12): 1377–87.
17. Boehm U, Bouloux PM, Dattani MT et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism – pathogenesis, diagnosis and treatment. Nat Rev Endocrin 2015; 11: 547–64.
18. Chernykh V.B., Rudneva S.A., Sorokina T.M. et al. Characteristics of spermatogenesis in infertile men with the AZFc region deletions. Andrology and Genital Surgery. 2014; 15 (2): 48–57 (in Russian).
19. Chernykh V.B. AZF deletions are common genetic cause of male infertility: current state of research. Problemy reproduktsii. 2009; 15 (1): 10–5 (in Russian).
20. Chernykh V.B., Stepanova A.A., Beskorovainaia T.S. et al. The frequency and spectrum of mutations and the IVS8-T polymorphism of the CFTR gene in Russian infertile men. Genetika. 2010; 46 (6): 844–52 (in Russian).
21. Repina S.A., Krasovskii S.A., Rozhivanov R.V. et al. Andrology examination of patients with pancreatic-sufficient and pancreatic-insufficient Cystic Fibrosis. Andrology and Genital Surgery. 2018; 19 (2): 31–9 (in Russian).
22. Shtaut M.I., Sorokina T.M., Kurilo L.F. et al. Comparative analysis of the results semen examination in patients with azoospermia caused by cystic fibrosis and congenital bilateral aplasia of vas deferens syndrome. Andrology and Genital Surgery. 2019; 20 (1): 82–90 (in Russian).
23. Repina S.A., Krasovskii S.A., Shmarina G.V. et al. Reproductive system status and the algorithm to solve fertility issues in men with cystic fibrosis. Almanac of Clinical Medicine. 2019; 47 (1): 26–37 (in Russian).
24. Bragina E.E., Sorokina T.M., Arifulin E.A., Kurilo L.F. Genetically determined patozoospermia. Literature review and research results. Andrology and Genital Surgery. 2015; 16 (3): 29–39 (in Russian).
25. Coutton C, Escoffier J, Martinez G et al. Teratozoospermia: spotlight on the main genetic actors in the human. Hum Reprod Update 2015; 21 (4): 455–85.
26. De Braekeleer M, Nguyen MH, Morel F, Perrin A. Genetic aspects of monomorphic teratozoospermia: a review. J Assist Reprod Genet 2015; 32 (4): 615–23.
27. Ben Khelifa M, Zouari R, Harbuz R et al. A new AURKC mutation causing macrozoospermia: implications for human spermatogenesis and clinical diagnosis. Mol Hum Reprod 2011; 17 (12): 762–8.
28. Ghédir H, Braham A, Viville S et al. Comparison of sperm morphology and nuclear sperm quality in SPATA16‐ and DPY19L2‐mutated globozoospermic patients. Andrologia 2019; 51 (6): e13277.
29. Tang S, Wang X, Li W et al. Biallelic mutations in CFAP43 and CFAP44 cause male infertility with multiple morphological abnormalities of the sperm flagella. Am J Hum Genet 2017; 100 (6): 854–64.
30. Chernykh V.B. Cystic Fibrosis gene and male infertility. Andrology and Genital Surgery. 2010; 4: 23–31 (in Russian).
2. Krausz C, Riera-Escamilla A. Genetics of male infertility. Nat Rev Urol 2018; 15: 369–84.
3. WHO guidelines for the study and treatment of human ejaculate. Transl. from English N.P. Makarova, scientific ed. L.F. Kurilo. 5th ed. Moscow: Capital Print, 2012 (in Russian).
4. Andreeva M.V., Khaiat S.Sh., Sorokina T.M. et al. Types of pathozoospermia in men with infertility in marriage аnd/or disorders of reproductive system. Andrology and Genital Surgery. 2017; 18 (2): 33–8 (in Russian).
5. Chernykh V.B., Iamandi T.A., Safina N.Iu. New molecular technologies in genetic diagnosis of male infertility. Andrology and Genital Surgery. 2017; 18 (1): 10–22 (in Russian).
6. Tuttelmann F, Simoni M et al. Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome. PLOS One 2011; 6 (4): e19426.
7. Solovova O.A., Chernykh V.B. Genetic causes of nonsyndromic forms of azoospermia and severe oligozoospermia in infertility men. Andrology and Genital Surgery. 2019; 20 (2): 16–28 (in Russian).
8. Safina N.Iu., Iamandi T.A., Chernykh V.B. et al. Genetic factors of male infertility, their combinations and the spermatological characteristics of men with fertility failures. Andrology and Genital Surgery. 2018; 19 (2): 40–51 (in Russian).
9. Olszewska M, Barciszewska MZ, Fraczek M et al. Global methylation status of sperm DNA in carriers of chromosome structural aberrations. Asian J Androl 2017; 19 (1): 117–24.
10. McKinlay Gardner RJ, Amor DJ. Gardner and Sutherland’s Chromosome Abnormalities and Genetic Counseling (5 ed.). Oxford University Press, 2018.
11. Chernykh V.B. Sex chromosomes abnormalities and CNVs, and their diagnosis. Medical Genetics. 2018; 17 (10): 8–14 (in Russian).
12. Bonomi M, Rochira V, Pasquali D et al. Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Invest 2017; 40: 123–34.
13. Vorona E, Zitzmann M, Gromoll J et al. Clinical, endocrinological, and epigenetic features of the 46,XX male syndrome, compared with 47,XXY Klinefelter patients. J Clin Endocrinol Metab 2007; 92: 3458–65.
14. Wong EC, Ferguson KA, Chow V, Ma S. Sperm aneuploidy and meiotic sex chromosome configurations in an infertile XYY male. Hum Reprod 2007; 23 (2): 374–8.
15. Maione L, Dwyer AA, Francou B et al. Genetics in endocrinology: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing. Eur J Endocrinol 2018; 178 (3): R55–R80.
16. Alkelai A, Olender T, Dode C et al. Next-generation sequencing of patients with congenital anosmia. Eur J Hum Genet 2017; 25 (12): 1377–87.
17. Boehm U, Bouloux PM, Dattani MT et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism – pathogenesis, diagnosis and treatment. Nat Rev Endocrin 2015; 11: 547–64.
18. Chernykh V.B., Rudneva S.A., Sorokina T.M. et al. Characteristics of spermatogenesis in infertile men with the AZFc region deletions. Andrology and Genital Surgery. 2014; 15 (2): 48–57 (in Russian).
19. Chernykh V.B. AZF deletions are common genetic cause of male infertility: current state of research. Problemy reproduktsii. 2009; 15 (1): 10–5 (in Russian).
20. Chernykh V.B., Stepanova A.A., Beskorovainaia T.S. et al. The frequency and spectrum of mutations and the IVS8-T polymorphism of the CFTR gene in Russian infertile men. Genetika. 2010; 46 (6): 844–52 (in Russian).
21. Repina S.A., Krasovskii S.A., Rozhivanov R.V. et al. Andrology examination of patients with pancreatic-sufficient and pancreatic-insufficient Cystic Fibrosis. Andrology and Genital Surgery. 2018; 19 (2): 31–9 (in Russian).
22. Shtaut M.I., Sorokina T.M., Kurilo L.F. et al. Comparative analysis of the results semen examination in patients with azoospermia caused by cystic fibrosis and congenital bilateral aplasia of vas deferens syndrome. Andrology and Genital Surgery. 2019; 20 (1): 82–90 (in Russian).
23. Repina S.A., Krasovskii S.A., Shmarina G.V. et al. Reproductive system status and the algorithm to solve fertility issues in men with cystic fibrosis. Almanac of Clinical Medicine. 2019; 47 (1): 26–37 (in Russian).
24. Bragina E.E., Sorokina T.M., Arifulin E.A., Kurilo L.F. Genetically determined patozoospermia. Literature review and research results. Andrology and Genital Surgery. 2015; 16 (3): 29–39 (in Russian).
25. Coutton C, Escoffier J, Martinez G et al. Teratozoospermia: spotlight on the main genetic actors in the human. Hum Reprod Update 2015; 21 (4): 455–85.
26. De Braekeleer M, Nguyen MH, Morel F, Perrin A. Genetic aspects of monomorphic teratozoospermia: a review. J Assist Reprod Genet 2015; 32 (4): 615–23.
27. Ben Khelifa M, Zouari R, Harbuz R et al. A new AURKC mutation causing macrozoospermia: implications for human spermatogenesis and clinical diagnosis. Mol Hum Reprod 2011; 17 (12): 762–8.
28. Ghédir H, Braham A, Viville S et al. Comparison of sperm morphology and nuclear sperm quality in SPATA16‐ and DPY19L2‐mutated globozoospermic patients. Andrologia 2019; 51 (6): e13277.
29. Tang S, Wang X, Li W et al. Biallelic mutations in CFAP43 and CFAP44 cause male infertility with multiple morphological abnormalities of the sperm flagella. Am J Hum Genet 2017; 100 (6): 854–64.
30. Chernykh V.B. Cystic Fibrosis gene and male infertility. Andrology and Genital Surgery. 2010; 4: 23–31 (in Russian).
Авторы
В.Б. Черных*1,2, О.А. Соловова1,3
1 ФГБНУ «Медико-генетический научный центр им. акад. Н.П. Бочкова», Москва, Россия;
2 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия;
3 ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского», Москва, Россия
*chernykh@med-gen.ru
1 ФГБНУ «Медико-генетический научный центр им. акад. Н.П. Бочкова», Москва, Россия;
2 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия;
3 ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского», Москва, Россия
*chernykh@med-gen.ru
________________________________________________
Vyacheslav B. Chernykh*1,2, Olga A. Solovova1,3
1 Bochkov Research Centre for Medical Genetics, Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia;
3 Vladimirskiy Moscow Regional Research Clinical Institute, Moscow, Russia
*chernykh@med-gen.ru
1 Bochkov Research Centre for Medical Genetics, Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia;
3 Vladimirskiy Moscow Regional Research Clinical Institute, Moscow, Russia
*chernykh@med-gen.ru
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