Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing.
NGS diagnosis
defects of primary spermatogenesis
hypogonadotropic hypogonadism
male infertility
primary ciliary dyskinesia
Journal
Life (Basel, Switzerland)
ISSN: 2075-1729
Titre abrégé: Life (Basel)
Pays: Switzerland
ID NLM: 101580444
Informations de publication
Date de publication:
15 Oct 2020
15 Oct 2020
Historique:
received:
21
09
2020
revised:
09
10
2020
accepted:
12
10
2020
entrez:
20
10
2020
pubmed:
21
10
2020
medline:
21
10
2020
Statut:
epublish
Résumé
Up to 15% of couples are infertile and male factor infertility accounts for approximately 50% of these cases. Male infertility is a multifactorial pathological condition. The genetic of male infertility is very complex and at least 2000 genes are involved in its etiology. Genetic testing by next-generation sequencing (NGS) technologies can be relevant for its diagnostic value in male infertile patients. Therefore, the aim of this study was to implement the diagnostic offer with the use of an NGS panel for the identification of genetic variants. We developed an NGS gene panel that we used in 22 male infertile patients. The panel consisted of 110 genes exploring the genetic causes of male infertility; namely spermatogenesis failure due to single-gene mutations, central hypogonadism, androgen insensitivity syndrome, congenital hypopituitarism, and primary ciliary dyskinesia. NGS and a subsequent sequencing of the positive pathogenic or likely pathogenic variants, 5 patients (23%) were found to have a molecular defect. In particular, pathogenic variants were identified in This extended NGS-based diagnostic approach may represent a useful tool for the diagnosis of male infertility. The development of a custom-made gene panel by NGS seems capable of reducing the proportion of male idiopathic infertility.
Sections du résumé
BACKGROUND
BACKGROUND
Up to 15% of couples are infertile and male factor infertility accounts for approximately 50% of these cases. Male infertility is a multifactorial pathological condition. The genetic of male infertility is very complex and at least 2000 genes are involved in its etiology. Genetic testing by next-generation sequencing (NGS) technologies can be relevant for its diagnostic value in male infertile patients. Therefore, the aim of this study was to implement the diagnostic offer with the use of an NGS panel for the identification of genetic variants.
METHODS
METHODS
We developed an NGS gene panel that we used in 22 male infertile patients. The panel consisted of 110 genes exploring the genetic causes of male infertility; namely spermatogenesis failure due to single-gene mutations, central hypogonadism, androgen insensitivity syndrome, congenital hypopituitarism, and primary ciliary dyskinesia.
RESULTS
RESULTS
NGS and a subsequent sequencing of the positive pathogenic or likely pathogenic variants, 5 patients (23%) were found to have a molecular defect. In particular, pathogenic variants were identified in
CONCLUSION
CONCLUSIONS
This extended NGS-based diagnostic approach may represent a useful tool for the diagnosis of male infertility. The development of a custom-made gene panel by NGS seems capable of reducing the proportion of male idiopathic infertility.
Identifiants
pubmed: 33076341
pii: life10100242
doi: 10.3390/life10100242
pmc: PMC7602585
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Provincia Autonoma di Trento
ID : dpg 1045/2017
Références
Nat Rev Urol. 2018 Jun;15(6):369-384
pubmed: 29622783
Asian J Androl. 2017 Jan-Feb;19(1):5-14
pubmed: 26680031
N Engl J Med. 2015 May 28;372(22):2097-107
pubmed: 25970010
J Vasc Surg. 2018 Mar;67(3):922-932.e11
pubmed: 28655553
Hum Reprod. 2017 Jan;32(1):18-31
pubmed: 27864361
Mol Hum Reprod. 2009 Mar;15(3):165-71
pubmed: 19168545
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Clin Genet. 2012 Mar;81(3):234-9
pubmed: 21554267
Reproduction. 2018 Jul;156(1):F29-F50
pubmed: 29945889
Eur J Hum Genet. 2018 Jan;26(1):12-33
pubmed: 29199274
Nat Genet. 2011 Jan;43(1):72-8
pubmed: 21131972
Clin Perinatol. 2018 Mar;45(1):75-91
pubmed: 29406008
Zhonghua Nan Ke Xue. 2013 May;19(5):414-7
pubmed: 23757962
Genet Test Mol Biomarkers. 2010 Dec;14(6):881-91
pubmed: 21158681
Eur Rev Med Pharmacol Sci. 2019 Sep;23(18):8139-8147
pubmed: 31599443
Hum Reprod Update. 2010 May-Jun;16(3):231-45
pubmed: 19934213
J Androl. 2010 Jan-Feb;31(1):79-85
pubmed: 19875494
Biomed Res Int. 2016;2016:7372362
pubmed: 26942199
J Clin Invest. 1992 Nov;90(5):2097-101
pubmed: 1430233
Fertil Steril. 2011 Jan;95(1):349-52, 352.e1-5
pubmed: 20864097
Reprod Med Biol. 2017 Mar 26;16(2):81-88
pubmed: 29259455
Nucleic Acids Res. 2015 Jan;43(Database issue):D789-98
pubmed: 25428349
Reprod Biomed Online. 2018 Mar;36(3):327-339
pubmed: 29336995
Arab J Urol. 2018 Feb 14;16(1):53-64
pubmed: 29713536
J Transl Med. 2019 Aug 14;17(1):267
pubmed: 31412890
Hum Reprod. 2019 May 1;34(5):932-941
pubmed: 30865283
Nat Med. 2008 Nov;14(11):1197-213
pubmed: 18989307
Curr Urol Rep. 2016 Oct;17(10):70
pubmed: 27502429
Saudi J Biol Sci. 2018 Jul;25(5):881-887
pubmed: 30108436
Cytogenet Genome Res. 2005;111(3-4):317-36
pubmed: 16192711
J Clin Endocrinol Metab. 1998 Dec;83(12):4177-88
pubmed: 9851748
Nature. 2008 Jun 12;453(7197):930-4
pubmed: 18454134
Hum Genet. 2019 Feb;138(2):125-140
pubmed: 30656449
PLoS Genet. 2008 Mar 28;4(3):e1000042
pubmed: 18369460
Sex Dev. 2008;2(4-5):200-9
pubmed: 18987494
Clin Endocrinol (Oxf). 2010 Apr;72(4):427-35
pubmed: 19719764
Fertil Steril. 2018 Jun;109(6):1105-1113
pubmed: 29935645
Curr Genet Med Rep. 2013 Dec 1;1(4):
pubmed: 24416713
Science. 2015 Jan 9;347(6218):1254806
pubmed: 25525159
J Biol Chem. 1992 Sep 5;267(25):17913-9
pubmed: 1517227
Am J Hum Genet. 2010 Oct 8;87(4):505-12
pubmed: 20887963
EMBO Mol Med. 2015 Jul 01;7(9):1198-210
pubmed: 26136358
Hum Reprod. 2003 Aug;18(8):1660-5
pubmed: 12871878
BMC Med Genet. 2018 Apr 16;19(1):63
pubmed: 29661171
Fertil Steril. 2015 Jul;104(1):163-9.e1
pubmed: 25989977
Appl Clin Genet. 2017 Sep 19;10:67-74
pubmed: 29033599
Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19238-43
pubmed: 23134727
Eur Respir J. 2017 Nov 9;50(5):
pubmed: 29122913
Asian J Androl. 2016 May-Jun;18(3):392-401
pubmed: 27056346
Hum Mutat. 2013 Mar;34(3):462-72
pubmed: 23255504
J Assist Reprod Genet. 2019 Aug;36(8):1683-1700
pubmed: 31273583
Hum Genet. 2020 Jul 7;:
pubmed: 32638125
Hum Reprod. 2007 Dec;22(12):3255-61
pubmed: 17940071
Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):507-515
pubmed: 29152903
Asian J Androl. 2020 Jul 10;:
pubmed: 32655042
Clin Chem Lab Med. 2017 Nov 27;56(1):40-50
pubmed: 28787268