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Spermatogenic failure 2(ASG; SPGF2)

MedGen UID:
400056
•Concept ID:
C1862459
•
Finding
Synonyms: ASPERMIOGENESIS FACTOR; SPGF2
 
Gene (location): MSH4 (1p31.1)
 
Monarch Initiative: MONDO:0007161
OMIM®: 108420

Definition

Spermatogenic failure-2 (SPGF2) is characterized by male infertility due to azoospermia (Tang et al., 2020; Akbari et al., 2021). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). [from OMIM]

Clinical features

From HPO
Azoospermia
MedGen UID:
2150
•Concept ID:
C0004509
•
Disease or Syndrome
Absence of any measurable level of sperm,whereby spermatozoa cannot be observed even after centrifugation of the semen pellet.
See: Feature record | Search on this feature
Male infertility
MedGen UID:
5796
•Concept ID:
C0021364
•
Disease or Syndrome
The inability of the male to effect fertilization of an ovum after a specified period of unprotected intercourse. Male sterility is permanent infertility.
See: Feature record | Search on this feature
Oligozoospermia
MedGen UID:
678638
•Concept ID:
C0868910
•
Finding
Reduced count of spermatozoa in the semen, defined as a sperm count below 20 million per milliliter semen.
See: Feature record | Search on this feature
Non-obstructive azoospermia
MedGen UID:
866757
•Concept ID:
C4021107
•
Disease or Syndrome
Absence of any measurable level of sperm in his semen, resulting from a defect in the production of spermatozoa in the testes. This can be differentiated from obstructive azoospermia on the basis of testicular biopsy.
See: Feature record | Search on this feature
Abnormal circulating luteinizing hormone concentration
MedGen UID:
663319
•Concept ID:
C0580438
•
Finding
An anomaly of the circulating level of luteinizing hormone (LH).
See: Feature record | Search on this feature
Abnormal circulating testosterone concentration
MedGen UID:
663334
•Concept ID:
C0580454
•
Finding
An anomalous concentration of testosterone in the blood.
See: Feature record | Search on this feature
Abnormal circulating follicle-stimulating hormone concentration
MedGen UID:
892827
•Concept ID:
C4072891
•
Finding
An anomaly of the circulating level of follicle-stimulating hormone (FSH).
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Toward clinical exomes in diagnostics and management of male infertility.
Lillepea K, Juchnewitsch AG, Kasak L, Valkna A, Dutta A, Pomm K, Poolamets O, Nagirnaja L, Tamp E, Mahyari E, Vihljajev V, Tjagur S, Papadimitriou S, Riera-Escamilla A, Versbraegen N, Farnetani G, Castillo-Madeen H, Sütt M, Kübarsepp V, Tennisberg S, Korrovits P, Krausz C, Aston KI, Lenaerts T, Conrad DF, Punab M, Laan M
Am J Hum Genet 2024 May 2;111(5):877-895. Epub 2024 Apr 12 doi: 10.1016/j.ajhg.2024.03.013. PMID: 38614076Free PMC Article
Clinical relevance of Y-linked CNV screening in male infertility: new insights based on the 8-year experience of a diagnostic genetic laboratory.
Lo Giacco D, Chianese C, Sánchez-Curbelo J, Bassas L, Ruiz P, Rajmil O, Sarquella J, Vives A, Ruiz-Castañé E, Oliva R, Ars E, Krausz C
Eur J Hum Genet 2014 Jun;22(6):754-61. Epub 2013 Nov 6 doi: 10.1038/ejhg.2013.253. PMID: 24193344Free PMC Article
Population study of causes, treatment, and outcome of infertility.
Hull MG, Glazener CM, Kelly NJ, Conway DI, Foster PA, Hinton RA, Coulson C, Lambert PA, Watt EM, Desai KM
Br Med J (Clin Res Ed) 1985 Dec 14;291(6510):1693-7. doi: 10.1136/bmj.291.6510.1693. PMID: 3935248Free PMC Article

Recent clinical studies

Etiology

Toward clinical exomes in diagnostics and management of male infertility.
Lillepea K, Juchnewitsch AG, Kasak L, Valkna A, Dutta A, Pomm K, Poolamets O, Nagirnaja L, Tamp E, Mahyari E, Vihljajev V, Tjagur S, Papadimitriou S, Riera-Escamilla A, Versbraegen N, Farnetani G, Castillo-Madeen H, Sütt M, Kübarsepp V, Tennisberg S, Korrovits P, Krausz C, Aston KI, Lenaerts T, Conrad DF, Punab M, Laan M
Am J Hum Genet 2024 May 2;111(5):877-895. Epub 2024 Apr 12 doi: 10.1016/j.ajhg.2024.03.013. PMID: 38614076Free PMC Article
Diverse monogenic subforms of human spermatogenic failure.
Nagirnaja L, Lopes AM, Charng WL, Miller B, Stakaitis R, Golubickaite I, Stendahl A, Luan T, Friedrich C, Mahyari E, Fadial E, Kasak L, Vigh-Conrad K, Oud MS, Xavier MJ, Cheers SR, James ER, Guo J, Jenkins TG, Riera-Escamilla A, Barros A, Carvalho F, Fernandes S, Gonçalves J, Gurnett CA, Jørgensen N, Jezek D, Jungheim ES, Kliesch S, McLachlan RI, Omurtag KR, Pilatz A, Sandlow JI, Smith J, Eisenberg ML, Hotaling JM, Jarvi KA, Punab M, Rajpert-De Meyts E, Carrell DT, Krausz C, Laan M, O'Bryan MK, Schlegel PN, Tüttelmann F, Veltman JA, Almstrup K, Aston KI, Conrad DF
Nat Commun 2022 Dec 26;13(1):7953. doi: 10.1038/s41467-022-35661-z. PMID: 36572685Free PMC Article
Spermatogenic failure and the Y chromosome.
Krausz C, Casamonti E
Hum Genet 2017 May;136(5):637-655. Epub 2017 Apr 29 doi: 10.1007/s00439-017-1793-8. PMID: 28456834
Klinefelter syndrome and TESE-ICSI.
Plotton I, Brosse A, Cuzin B, Lejeune H
Ann Endocrinol (Paris) 2014 May;75(2):118-25. Epub 2014 Apr 29 doi: 10.1016/j.ando.2014.04.004. PMID: 24786702
Genetics of spermatogenic failure.
Huang WJ, Yen PH
Sex Dev 2008;2(4-5):251-9. Epub 2008 Nov 5 doi: 10.1159/000152041. PMID: 18987499

Diagnosis

Toward clinical exomes in diagnostics and management of male infertility.
Lillepea K, Juchnewitsch AG, Kasak L, Valkna A, Dutta A, Pomm K, Poolamets O, Nagirnaja L, Tamp E, Mahyari E, Vihljajev V, Tjagur S, Papadimitriou S, Riera-Escamilla A, Versbraegen N, Farnetani G, Castillo-Madeen H, Sütt M, Kübarsepp V, Tennisberg S, Korrovits P, Krausz C, Aston KI, Lenaerts T, Conrad DF, Punab M, Laan M
Am J Hum Genet 2024 May 2;111(5):877-895. Epub 2024 Apr 12 doi: 10.1016/j.ajhg.2024.03.013. PMID: 38614076Free PMC Article
Diverse monogenic subforms of human spermatogenic failure.
Nagirnaja L, Lopes AM, Charng WL, Miller B, Stakaitis R, Golubickaite I, Stendahl A, Luan T, Friedrich C, Mahyari E, Fadial E, Kasak L, Vigh-Conrad K, Oud MS, Xavier MJ, Cheers SR, James ER, Guo J, Jenkins TG, Riera-Escamilla A, Barros A, Carvalho F, Fernandes S, Gonçalves J, Gurnett CA, Jørgensen N, Jezek D, Jungheim ES, Kliesch S, McLachlan RI, Omurtag KR, Pilatz A, Sandlow JI, Smith J, Eisenberg ML, Hotaling JM, Jarvi KA, Punab M, Rajpert-De Meyts E, Carrell DT, Krausz C, Laan M, O'Bryan MK, Schlegel PN, Tüttelmann F, Veltman JA, Almstrup K, Aston KI, Conrad DF
Nat Commun 2022 Dec 26;13(1):7953. doi: 10.1038/s41467-022-35661-z. PMID: 36572685Free PMC Article
New insights into the genetics of spermatogenic failure: a review of the literature.
Cannarella R, Condorelli RA, Duca Y, La Vignera S, Calogero AE
Hum Genet 2019 Feb;138(2):125-140. Epub 2019 Jan 17 doi: 10.1007/s00439-019-01974-1. PMID: 30656449
Spermatogenic failure and the Y chromosome.
Krausz C, Casamonti E
Hum Genet 2017 May;136(5):637-655. Epub 2017 Apr 29 doi: 10.1007/s00439-017-1793-8. PMID: 28456834
Polymerase chain reaction screening for Y chromosome microdeletions: a first step towards the diagnosis of genetically-determined spermatogenic failure in men.
Qureshi SJ, Ross AR, Ma K, Cooke HJ, Intyre MA, Chandley AC, Hargreave TB
Mol Hum Reprod 1996 Oct;2(10):775-9. doi: 10.1093/molehr/2.10.775. PMID: 9239696

Therapy

External and Genetic Conditions Determining Male Infertility.
Kamiński P, Baszyński J, Jerzak I, Kavanagh BP, Nowacka-Chiari E, Polanin M, Szymański M, Woźniak A, Kozera W
Int J Mol Sci 2020 Jul 24;21(15) doi: 10.3390/ijms21155274. PMID: 32722328Free PMC Article
Antiretroviral Therapy and Alcohol Interactions: X-raying Testicular and Seminal Parameters Under the HAART Era.
Ogedengbe OO, Naidu ECS, Azu OO
Eur J Drug Metab Pharmacokinet 2018 Apr;43(2):121-135. doi: 10.1007/s13318-017-0438-6. PMID: 28956285
Hydrogen Sulfide As a Potential Target in Preventing Spermatogenic Failure and Testicular Dysfunction.
Wang J, Wang W, Li S, Han Y, Zhang P, Meng G, Xiao Y, Xie L, Wang X, Sha J, Chen Q, Moore PK, Wang R, Xiang W, Ji Y
Antioxid Redox Signal 2018 Jun 1;28(16):1447-1462. Epub 2017 Oct 16 doi: 10.1089/ars.2016.6968. PMID: 28537489
Y chromosome b2/b3 deletions and male infertility: A comprehensive meta-analysis, trial sequential analysis and systematic review.
Bansal SK, Gupta G, Rajender S
Mutat Res Rev Mutat Res 2016 Apr-Jun;768:78-90. Epub 2016 May 4 doi: 10.1016/j.mrrev.2016.04.007. PMID: 27234565
Klinefelter syndrome and TESE-ICSI.
Plotton I, Brosse A, Cuzin B, Lejeune H
Ann Endocrinol (Paris) 2014 May;75(2):118-25. Epub 2014 Apr 29 doi: 10.1016/j.ando.2014.04.004. PMID: 24786702

Prognosis

Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men.
Fietz D, Sgaier R, O'Donnell L, Stanton PG, Dagley LF, Webb AI, Schuppe HC, Diemer T, Pilatz A
Front Endocrinol (Lausanne) 2024;15:1327800. Epub 2024 Apr 9 doi: 10.3389/fendo.2024.1327800. PMID: 38654926Free PMC Article
Consequences of Y chromosome microdeletions beyond male infertility.
Colaco S, Modi D
J Assist Reprod Genet 2019 Jul;36(7):1329-1337. Epub 2019 Jun 18 doi: 10.1007/s10815-019-01492-z. PMID: 31214882Free PMC Article
Spermatogenic failure and the Y chromosome.
Krausz C, Casamonti E
Hum Genet 2017 May;136(5):637-655. Epub 2017 Apr 29 doi: 10.1007/s00439-017-1793-8. PMID: 28456834
45,X karyotype in an infertile man: how is this possible?
Amaro A, Mafra FA, Valada Pane CE, Kulikowski LD, Bianco B, Barbosa CP, Christofolini DM
Urol Int 2015;94(4):488-90. Epub 2014 Aug 20 doi: 10.1159/000365010. PMID: 25170625
Feasibility of global gene expression analysis in testicular biopsies from infertile men.
Fox MS, Ares VX, Turek PJ, Haqq C, Reijo Pera RA
Mol Reprod Dev 2003 Dec;66(4):403-21. doi: 10.1002/mrd.10364. PMID: 14579417

Clinical prediction guides

Toward clinical exomes in diagnostics and management of male infertility.
Lillepea K, Juchnewitsch AG, Kasak L, Valkna A, Dutta A, Pomm K, Poolamets O, Nagirnaja L, Tamp E, Mahyari E, Vihljajev V, Tjagur S, Papadimitriou S, Riera-Escamilla A, Versbraegen N, Farnetani G, Castillo-Madeen H, Sütt M, Kübarsepp V, Tennisberg S, Korrovits P, Krausz C, Aston KI, Lenaerts T, Conrad DF, Punab M, Laan M
Am J Hum Genet 2024 May 2;111(5):877-895. Epub 2024 Apr 12 doi: 10.1016/j.ajhg.2024.03.013. PMID: 38614076Free PMC Article
Consequences of Y chromosome microdeletions beyond male infertility.
Colaco S, Modi D
J Assist Reprod Genet 2019 Jul;36(7):1329-1337. Epub 2019 Jun 18 doi: 10.1007/s10815-019-01492-z. PMID: 31214882Free PMC Article
Spermatogenic failure and the Y chromosome.
Krausz C, Casamonti E
Hum Genet 2017 May;136(5):637-655. Epub 2017 Apr 29 doi: 10.1007/s00439-017-1793-8. PMID: 28456834
Loss of the AZFc region due to a human Y-chromosome microdeletion in infertile male patients.
Pandey LK, Pandey S, Gupta J, Saxena AK
Genet Mol Res 2010 Jun 29;9(2):1267-73. doi: 10.4238/vol9-2gmr836. PMID: 20603812
Mutations in the protamine locus: association with spermatogenic failure?
Imken L, Rouba H, El Houate B, Louanjli N, Barakat A, Chafik A, McElreavey K
Mol Hum Reprod 2009 Nov;15(11):733-8. Epub 2009 Jul 14 doi: 10.1093/molehr/gap056. PMID: 19602509

Recent systematic reviews

The impact of vincristine on testicular development and function in childhood cancer.
Clark I, Brougham MFH, Spears N, Mitchell RT
Hum Reprod Update 2023 Mar 1;29(2):233-245. doi: 10.1093/humupd/dmac039. PMID: 36495566Free PMC Article
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its effect on gametogenesis and early pregnancy.
Singh B, Gornet M, Sims H, Kisanga E, Knight Z, Segars J
Am J Reprod Immunol 2020 Nov;84(5):e13351. Epub 2020 Oct 9 doi: 10.1111/aji.13351. PMID: 32969123Free PMC Article
Y chromosome b2/b3 deletions and male infertility: A comprehensive meta-analysis, trial sequential analysis and systematic review.
Bansal SK, Gupta G, Rajender S
Mutat Res Rev Mutat Res 2016 Apr-Jun;768:78-90. Epub 2016 May 4 doi: 10.1016/j.mrrev.2016.04.007. PMID: 27234565

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