Mutations in the stromal antigen 3 (STAG3) gene cause male infertility due to meiotic arrest
Abstract STUDY QUESTION Are sequence variants in the stromal antigen 3 (STAG3) gene a cause for non-obstructive azoospermia (NOA) in infertile human males? SUMMARY ANSWER Sequence variants affecting protein function of STAG3 cause male infertility due to meiotic arrest. WHAT IS KNOWN ALREADY In both...
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Published in | Human reproduction (Oxford) Vol. 34; no. 11; pp. 2112 - 2119 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Oxford University Press
01.11.2019
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Abstract | Abstract
STUDY QUESTION
Are sequence variants in the stromal antigen 3 (STAG3) gene a cause for non-obstructive azoospermia (NOA) in infertile human males?
SUMMARY ANSWER
Sequence variants affecting protein function of STAG3 cause male infertility due to meiotic arrest.
WHAT IS KNOWN ALREADY
In both women and men, STAG3 encodes for a meiosis-specific protein that is crucial for the functionality of meiotic cohesin complexes. Sequence variants in STAG3 have been reported to cause meiotic arrest in male and female mice and premature ovarian failure in human females, but not in infertile human males so far.
STUDY DESIGN, SIZE, DURATION
The full coding region of STAG3 was sequenced directly in a cohort of 28 men with NOA due to meiotic arrest. In addition, a larger group of 275 infertile men that underwent whole-exome sequencing (WES) was screened for potential STAG3 sequence variants. Furthermore, meiotic spreads, immunohistochemistry, WES and population sampling probability (PSAP) have been conducted in the index case.
PARTICIPANTS/MATERIALS, SETTING, METHODS
This study included 28 infertile but otherwise healthy human males who underwent Sanger sequencing of the full coding region of STAG3. Additionally, WES data of 275 infertile human males with different infertility phenotypes have been screened for relevant STAG3 variants. All participants underwent karyotype analysis and azoospermia factor (AZF) screening in advance. In the index patient, segregation analysis, WES data, PSAP, lab parameters, testis histology and nuclear spreads have been added to suplort the findings.
MAIN RESULTS AND THE ROLE OF CHANCE
Two compound-heterozygous variants in STAG3 (c.[1262T>G];[1312C>T], p.[(Leu421Arg)];[(Arg438Ter)]) have been found to cause male infertility due to complete bilateral meiotic arrest in an otherwise healthy human male. Compound heterozygosity was confirmed by Sanger sequencing of the parents and the patient’s brother. Other variants which may affect spermatogenesis have been ruled out through analysis of the patient’s WES data and application of the PSAP pipeline. As expected from Stag3 knockout-mice meiotic spreads, germ cells did not develop further than zygotene and showed drastic chromosome aberrations. No rare variants in STAG3 were found in the 275 infertile males with other phenotypes. Our results indicate that STAG3 variants that negatively affect its protein function are a rare cause of NOA (<1% of cases).
LIMITATIONS, REASONS FOR CAUTION
We identified only one patient with compound-heterozygous variants in STAG3 causing NOA due to meiotic arrest. Future studies should evaluate STAG3 variants in larger cohorts to support this finding.
WIDER IMPLICATIONS OF THE FINDINGS
Identification of STAG3 sequence variants in infertile human males should improve genetic counselling as well as diagnostics and treatment. Especially before testicular sperm extraction (TESE) for ICSI, STAG3 variants should be ruled out to prevent unnecessary interventions with frustrating outcomes for both patients and clinicians.
STUDY FUNDING/COMPETING INTEREST(S)
This work was carried out within the frame of the German Research Foundation (DFG) Clinical Research Unit ‘Male Germ Cells: from Genes to Function’ (CRU326). Work in the laboratory of R.J. is supported by a grant of the European Union H2020 program GermAge. The authors declare no conflicts of interest.
TRIAL REGISTRATION NUMBER
Not applicable. |
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AbstractList | Abstract
STUDY QUESTION
Are sequence variants in the stromal antigen 3 (STAG3) gene a cause for non-obstructive azoospermia (NOA) in infertile human males?
SUMMARY ANSWER
Sequence variants affecting protein function of STAG3 cause male infertility due to meiotic arrest.
WHAT IS KNOWN ALREADY
In both women and men, STAG3 encodes for a meiosis-specific protein that is crucial for the functionality of meiotic cohesin complexes. Sequence variants in STAG3 have been reported to cause meiotic arrest in male and female mice and premature ovarian failure in human females, but not in infertile human males so far.
STUDY DESIGN, SIZE, DURATION
The full coding region of STAG3 was sequenced directly in a cohort of 28 men with NOA due to meiotic arrest. In addition, a larger group of 275 infertile men that underwent whole-exome sequencing (WES) was screened for potential STAG3 sequence variants. Furthermore, meiotic spreads, immunohistochemistry, WES and population sampling probability (PSAP) have been conducted in the index case.
PARTICIPANTS/MATERIALS, SETTING, METHODS
This study included 28 infertile but otherwise healthy human males who underwent Sanger sequencing of the full coding region of STAG3. Additionally, WES data of 275 infertile human males with different infertility phenotypes have been screened for relevant STAG3 variants. All participants underwent karyotype analysis and azoospermia factor (AZF) screening in advance. In the index patient, segregation analysis, WES data, PSAP, lab parameters, testis histology and nuclear spreads have been added to suplort the findings.
MAIN RESULTS AND THE ROLE OF CHANCE
Two compound-heterozygous variants in STAG3 (c.[1262T>G];[1312C>T], p.[(Leu421Arg)];[(Arg438Ter)]) have been found to cause male infertility due to complete bilateral meiotic arrest in an otherwise healthy human male. Compound heterozygosity was confirmed by Sanger sequencing of the parents and the patient’s brother. Other variants which may affect spermatogenesis have been ruled out through analysis of the patient’s WES data and application of the PSAP pipeline. As expected from Stag3 knockout-mice meiotic spreads, germ cells did not develop further than zygotene and showed drastic chromosome aberrations. No rare variants in STAG3 were found in the 275 infertile males with other phenotypes. Our results indicate that STAG3 variants that negatively affect its protein function are a rare cause of NOA (<1% of cases).
LIMITATIONS, REASONS FOR CAUTION
We identified only one patient with compound-heterozygous variants in STAG3 causing NOA due to meiotic arrest. Future studies should evaluate STAG3 variants in larger cohorts to support this finding.
WIDER IMPLICATIONS OF THE FINDINGS
Identification of STAG3 sequence variants in infertile human males should improve genetic counselling as well as diagnostics and treatment. Especially before testicular sperm extraction (TESE) for ICSI, STAG3 variants should be ruled out to prevent unnecessary interventions with frustrating outcomes for both patients and clinicians.
STUDY FUNDING/COMPETING INTEREST(S)
This work was carried out within the frame of the German Research Foundation (DFG) Clinical Research Unit ‘Male Germ Cells: from Genes to Function’ (CRU326). Work in the laboratory of R.J. is supported by a grant of the European Union H2020 program GermAge. The authors declare no conflicts of interest.
TRIAL REGISTRATION NUMBER
Not applicable. STUDY QUESTIONAre sequence variants in the stromal antigen 3 (STAG3) gene a cause for non-obstructive azoospermia (NOA) in infertile human males? SUMMARY ANSWERSequence variants affecting protein function of STAG3 cause male infertility due to meiotic arrest. WHAT IS KNOWN ALREADYIn both women and men, STAG3 encodes for a meiosis-specific protein that is crucial for the functionality of meiotic cohesin complexes. Sequence variants in STAG3 have been reported to cause meiotic arrest in male and female mice and premature ovarian failure in human females, but not in infertile human males so far. STUDY DESIGN, SIZE, DURATIONThe full coding region of STAG3 was sequenced directly in a cohort of 28 men with NOA due to meiotic arrest. In addition, a larger group of 275 infertile men that underwent whole-exome sequencing (WES) was screened for potential STAG3 sequence variants. Furthermore, meiotic spreads, immunohistochemistry, WES and population sampling probability (PSAP) have been conducted in the index case. PARTICIPANTS/MATERIALS, SETTING, METHODSThis study included 28 infertile but otherwise healthy human males who underwent Sanger sequencing of the full coding region of STAG3. Additionally, WES data of 275 infertile human males with different infertility phenotypes have been screened for relevant STAG3 variants. All participants underwent karyotype analysis and azoospermia factor (AZF) screening in advance. In the index patient, segregation analysis, WES data, PSAP, lab parameters, testis histology and nuclear spreads have been added to suplort the findings. MAIN RESULTS AND THE ROLE OF CHANCETwo compound-heterozygous variants in STAG3 (c.[1262T>G];[1312C>T], p.[(Leu421Arg)];[(Arg438Ter)]) have been found to cause male infertility due to complete bilateral meiotic arrest in an otherwise healthy human male. Compound heterozygosity was confirmed by Sanger sequencing of the parents and the patient's brother. Other variants which may affect spermatogenesis have been ruled out through analysis of the patient's WES data and application of the PSAP pipeline. As expected from Stag3 knockout-mice meiotic spreads, germ cells did not develop further than zygotene and showed drastic chromosome aberrations. No rare variants in STAG3 were found in the 275 infertile males with other phenotypes. Our results indicate that STAG3 variants that negatively affect its protein function are a rare cause of NOA (<1% of cases). LIMITATIONS, REASONS FOR CAUTIONWe identified only one patient with compound-heterozygous variants in STAG3 causing NOA due to meiotic arrest. Future studies should evaluate STAG3 variants in larger cohorts to support this finding. WIDER IMPLICATIONS OF THE FINDINGSIdentification of STAG3 sequence variants in infertile human males should improve genetic counselling as well as diagnostics and treatment. Especially before testicular sperm extraction (TESE) for ICSI, STAG3 variants should be ruled out to prevent unnecessary interventions with frustrating outcomes for both patients and clinicians. STUDY FUNDING/COMPETING INTEREST(S)This work was carried out within the frame of the German Research Foundation (DFG) Clinical Research Unit 'Male Germ Cells: from Genes to Function' (CRU326). Work in the laboratory of R.J. is supported by a grant of the European Union H2020 program GermAge. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBERNot applicable. |
Author | Kliesch, S Friedrich, C Wöste, M Jessberger, R Röpke, A Biswas, U van der Bijl, N Tüttelmann, F |
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Cites_doi | 10.1002/embj.201387330 10.1371/journal.pgen.1006389 10.1016/j.molmed.2006.05.005 10.1083/jcb.200808016 10.1056/NEJMoa1309635 10.1038/ejhg.2012.290 10.18632/oncotarget.13684 10.1007/s11825-018-0181-7 10.1016/j.cub.2017.12.020 10.1038/ng.3697 10.1016/j.ajhg.2018.07.005 10.1038/gim.2015.30 10.1093/hmg/ddu051 10.1111/j.1365-2605.2010.01087.x 10.1371/journal.pgen.1004413 10.1093/humrep/dez042 10.1534/g3.116.029462 10.1186/s12958-015-0032-1 10.1242/dev.160614 10.1002/embj.201387329 10.1016/j.fertnstert.2015.04.020 10.1093/humrep/deq180 10.1056/NEJMoa1406192 |
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Keywords | meiotic arrest sequence analysis non-obstructive azoospermia STAG3 male infertility |
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References | Richards (2019110413460118800_ref14) 2015; 17 Röpke (2019110413460118800_ref16) 2013; 21 Yatsenko (2019110413460118800_ref24) 2015; 372 Caburet (2019110413460118800_ref5) 2014; 370 Ventimiglia (2019110413460118800_ref20) 2015; 104 Riera-Escamilla (2019110413460118800_ref15) 2019; 34 Hopkins (2019110413460118800_ref9) 2014; 10 Kasak (2019110413460118800_ref11) 2018; 103 He (2019110413460118800_ref8) 2017 Jan (2019110413460118800_ref10) 2018; 145 Zhang (2019110413460118800_ref25) 2017; 8 Biswas (2019110413460118800_ref3) 2016; 12 Adelfalk (2019110413460118800_ref1) 2009; 187 Garcia-Cruz (2019110413460118800_ref7) 2010; 25 Llano (2019110413460118800_ref13) 2014; 23 Fukuda (2019110413460118800_ref6) 2014; 33 Agarwal (2019110413460118800_ref2) 2015; 13 Ward (2019110413460118800_ref21) 2016; 6 Tüttelmann (2019110413460118800_ref19) 2011; 34 Kuzmiak (2019110413460118800_ref12) 2006; 12 Winters (2019110413460118800_ref23) 2014; 33 Tüttelmann (2019110413460118800_ref18) 2018; 30 Tournaye (2019110413460118800_ref17); 2016 Wilfert (2019110413460118800_ref22) 2016; 48 Biswas (2019110413460118800_ref4) 2018; 28 |
References_xml | – volume: 33 start-page: 1256 year: 2014 ident: 2019110413460118800_ref23 article-title: Meiotic cohesin STAG3 is required for chromosome axis formation and sister chromatid cohesion publication-title: EMBO J doi: 10.1002/embj.201387330 contributor: fullname: Winters – volume: 12 year: 2016 ident: 2019110413460118800_ref3 article-title: Distinct roles of meiosis-specific cohesin complexes in mammalian spermatogenesis publication-title: PLoS Genet doi: 10.1371/journal.pgen.1006389 contributor: fullname: Biswas – volume: 12 start-page: 306 year: 2006 ident: 2019110413460118800_ref12 article-title: Applying nonsense-mediated mRNA decay research to the clinic: progress and challenges publication-title: Trends Mol Med doi: 10.1016/j.molmed.2006.05.005 contributor: fullname: Kuzmiak – volume: 2016 start-page: 544 ident: 2019110413460118800_ref17 article-title: Novel concepts in the aetiology of male reproductive impairment publication-title: Lancet Diabetes contributor: fullname: Tournaye – volume: 187 start-page: 185 year: 2009 ident: 2019110413460118800_ref1 article-title: Cohesin SMC1beta protects telomeres in meiocytes publication-title: J Cell Biol doi: 10.1083/jcb.200808016 contributor: fullname: Adelfalk – volume: 370 start-page: 943 year: 2014 ident: 2019110413460118800_ref5 article-title: Mutant cohesin in premature ovarian failure publication-title: N Engl J Med doi: 10.1056/NEJMoa1309635 contributor: fullname: Caburet – volume: 21 start-page: 1012 year: 2013 ident: 2019110413460118800_ref16 article-title: Comprehensive sequence analysis of the NR5A1 gene encoding steroidogenic factor 1 in a large group of infertile males publication-title: Eur J Hum Genet doi: 10.1038/ejhg.2012.290 contributor: fullname: Röpke – start-page: 340 year: 2017 ident: 2019110413460118800_ref8 article-title: Whole-exome sequencing identifies a homozygous donor splice-site mutation in STAG3 that causes primary ovarian insufficiency publication-title: Clin Genet contributor: fullname: He – volume: 8 start-page: 1593 year: 2017 ident: 2019110413460118800_ref25 article-title: Stag3 regulates microtubule stability to maintain euploidy during mouse oocyte meiotic maturation publication-title: Oncotarget doi: 10.18632/oncotarget.13684 contributor: fullname: Zhang – volume: 30 start-page: 12 year: 2018 ident: 2019110413460118800_ref18 article-title: Disorders of spermatogenesis: perspectives for novel genetic diagnostics after 20 years of unchanged routine publication-title: Medizinische Genetik doi: 10.1007/s11825-018-0181-7 contributor: fullname: Tüttelmann – volume: 28 start-page: 249 year: 2018 ident: 2019110413460118800_ref4 article-title: SMC1α substitutes for many meiotic functions of SMC1β but cannot protect telomeres from damage publication-title: Current Biol doi: 10.1016/j.cub.2017.12.020 contributor: fullname: Biswas – volume: 48 start-page: 1455 year: 2016 ident: 2019110413460118800_ref22 article-title: Genome-wide significance testing of variation from single case exomes publication-title: Nat Genet doi: 10.1038/ng.3697 contributor: fullname: Wilfert – volume: 103 start-page: 200 year: 2018 ident: 2019110413460118800_ref11 article-title: Bi-allelic recessive loss-of-function variants in FANCM cause non-obstructive azoospermia publication-title: Am J Hum Genet doi: 10.1016/j.ajhg.2018.07.005 contributor: fullname: Kasak – volume: 17 start-page: 405 year: 2015 ident: 2019110413460118800_ref14 article-title: ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology publication-title: Genet Med doi: 10.1038/gim.2015.30 contributor: fullname: Richards – volume: 23 start-page: 3421 year: 2014 ident: 2019110413460118800_ref13 article-title: STAG3 is a strong candidate gene for male infertility publication-title: Hum Mol Genet doi: 10.1093/hmg/ddu051 contributor: fullname: Llano – volume: 34 start-page: 291 year: 2011 ident: 2019110413460118800_ref19 article-title: Clinical experience with azoospermia: aetiology and chances for spermatozoa detection upon biopsy publication-title: Int J Androl doi: 10.1111/j.1365-2605.2010.01087.x contributor: fullname: Tüttelmann – volume: 10 year: 2014 ident: 2019110413460118800_ref9 article-title: Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes publication-title: PLoS Genet doi: 10.1371/journal.pgen.1004413 contributor: fullname: Hopkins – volume: 34 start-page: 978 year: 2019 ident: 2019110413460118800_ref15 article-title: Sequencing of a ‘mouse azoospermia’ gene panel in azoospermic men: identification of RNF212 and STAG3 mutations as novel genetic causes of meiotic arrest publication-title: Hum Reprod doi: 10.1093/humrep/dez042 contributor: fullname: Riera-Escamilla – volume: 6 start-page: 1713 year: 2016 ident: 2019110413460118800_ref21 article-title: Genetic interactions between the meiosis-specific cohesin components, STAG3, REC8, and RAD21L publication-title: G3 Bethesda doi: 10.1534/g3.116.029462 contributor: fullname: Ward – volume: 13 start-page: 37 year: 2015 ident: 2019110413460118800_ref2 article-title: A unique view on male infertility around the globe publication-title: Reprod Biol Endocrinol doi: 10.1186/s12958-015-0032-1 contributor: fullname: Agarwal – volume: 145 year: 2018 ident: 2019110413460118800_ref10 article-title: Distinct prophase arrest mechanisms in human male meiosis publication-title: Development doi: 10.1242/dev.160614 contributor: fullname: Jan – volume: 33 start-page: 1243 year: 2014 ident: 2019110413460118800_ref6 article-title: STAG3-mediated stabilization of REC8 cohesin complexes promotes chromosome synapsis during meiosis publication-title: EMBO J doi: 10.1002/embj.201387329 contributor: fullname: Fukuda – volume: 104 start-page: 48 year: 2015 ident: 2019110413460118800_ref20 article-title: Infertility as a proxy of general male health: results of a cross-sectional survey publication-title: Fertil Steril doi: 10.1016/j.fertnstert.2015.04.020 contributor: fullname: Ventimiglia – volume: 25 start-page: 2316 year: 2010 ident: 2019110413460118800_ref7 article-title: Dynamics of cohesin proteins REC8, STAG3, SMC1 beta and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes publication-title: Hum Reprod doi: 10.1093/humrep/deq180 contributor: fullname: Garcia-Cruz – volume: 372 start-page: 2097 year: 2015 ident: 2019110413460118800_ref24 article-title: X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men publication-title: N Engl J Med doi: 10.1056/NEJMoa1406192 contributor: fullname: Yatsenko |
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STUDY QUESTION
Are sequence variants in the stromal antigen 3 (STAG3) gene a cause for non-obstructive azoospermia (NOA) in infertile human males?... STUDY QUESTIONAre sequence variants in the stromal antigen 3 (STAG3) gene a cause for non-obstructive azoospermia (NOA) in infertile human males? SUMMARY... |
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