Evaluation of an Updated Gene Panel as a Diagnostic Tool for Both Male and Female Infertility.
Female infertility
Gene panel
Male infertility
Reproductive genetics
Journal
Reproductive sciences (Thousand Oaks, Calif.)
ISSN: 1933-7205
Titre abrégé: Reprod Sci
Pays: United States
ID NLM: 101291249
Informations de publication
Date de publication:
25 Apr 2024
25 Apr 2024
Historique:
received:
08
01
2024
accepted:
02
04
2024
medline:
26
4
2024
pubmed:
26
4
2024
entrez:
25
4
2024
Statut:
aheadofprint
Résumé
In recent years, an increasing number of genes associated with male and female infertility have been identified. The genetics of infertility is no longer limited to the analysis of karyotypes or specific genes, and it is now possible to analyse several dozen infertility genes simultaneously. Here, we present the diagnostic activity over the past two years including 140 patients (63 women and 77 men). Targeted sequencing revealed causative variants in 17 patients, representing an overall diagnostic rate of 12.1%, with prevalence rates in females and males of 11% and 13%, respectively. The gene-disease relationship (GDR) was re-evaluated for genes due to the addition of new patients and/or variants in the actual study. Five genes changed categories: two female genes (MEIOB and TBPL2) moved from limited to moderate; two male genes (SOHLH1 and GALNTL5) moved from no evidence to strong and from limited to moderate; and SEPTIN12, which was unable to classify male infertility, was reclassified as limited. Many infertility genes have yet to be identified. With the increasing integration of genetics in reproductive medicine, the scope of intervention extends to include other family members, in addition to individual patients or couples. Genetic counselling consultations and appropriate staffing will need to be established in fertility centres. Trial registration number: Not applicable.
Identifiants
pubmed: 38664359
doi: 10.1007/s43032-024-01553-4
pii: 10.1007/s43032-024-01553-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.
Références
Lyon A, Bilton D. Fertility issues in cystic fibrosis. Paediatr Respir Rev. 2002;3:236–40. https://doi.org/10.1016/s1526-0542(02)00184-7 .
doi: 10.1016/s1526-0542(02)00184-7
pubmed: 12376060
Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461:272–276. doi: https://doi.org/10.1038/nature08250 .
Okutman O, Rhouma MB, Benkhalifa M, Muller J, Viville S. ‘Genetic evaluation of patients with non-syndromic male infertility. J Assist Reprod Genet. 2018;35:1939–51. https://doi.org/10.1007/s10815-018-1301-7 .
doi: 10.1007/s10815-018-1301-7
pubmed: 30259277
pmcid: 6240550
Ghieh F, Barbotin AL, Swierkowski-Blanchard N, Leroy C, Fortemps J, Gerault C, et al. Whole-exome sequencing in patients with maturation arrest: a potential additional diagnostic tool for prevention of recurrent negative testicular sperm extraction outcomes. Hum Reprod. 2022;37:1334–50. https://doi.org/10.1093/humrep/deac057 .
doi: 10.1093/humrep/deac057
pubmed: 35413094
pmcid: 9156845
Kherraf ZE, Cazin C, Bouker A, Fourati Ben Mustapha S, Hennebicq S, Septier A, et al. Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia. Am J Hum Genet. 2022;109:508–517. doi: https://doi.org/10.1016/j.ajhg.2022.01.011 .
Patel B, Parets S, Akana M, Kellogg G, Jansen M, Chang C, et al. Comprehensive genetic testing for female and male infertility using next-generation sequencing. J Assist Reprod Genet. 2018;35:1489–96. https://doi.org/10.1007/s10815-018-1204-7 .
doi: 10.1007/s10815-018-1204-7
pubmed: 29779145
pmcid: 6086787
Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015;13:37. https://doi.org/10.1186/s12958-015-0032-1 .
doi: 10.1186/s12958-015-0032-1
pubmed: 25928197
pmcid: 4424520
Gelbaya TA, Potdar N, Jeve YB, Nardo LG. Definition and epidemiology of unexplained infertility. Obstet Gynecol Surv. 2014;69:109–15. https://doi.org/10.1097/OGX.0000000000000043 .
doi: 10.1097/OGX.0000000000000043
pubmed: 25112489
Krausz C. Male infertility: pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinol Metab. 2011;25:271–85. https://doi.org/10.1016/j.beem.2010.08.006 .
doi: 10.1016/j.beem.2010.08.006
pubmed: 21397198
Okutman O, Tarabeux J, Muller J, Viville S. Evaluation of a custom design gene panel as a diagnostic tool for human non-syndromic infertility. Genes (Basel). 2021;12:410. https://doi.org/10.3390/genes12030410 .
doi: 10.3390/genes12030410
pubmed: 33809228
Oud MS, Volozonoka L, Smits RM, Vissers LELM, Ramos L, Veltman JA. A systematic review and standardized clinical validity assessment of male infertility genes. Hum Reprod. 2019;34:932–41. https://doi.org/10.1093/humrep/dez022 .
doi: 10.1093/humrep/dez022
pubmed: 30865283
pmcid: 6505449
Geoffroy V, Pizot C, Redin C, Piton A, Vasli N, et al. VaRank: a simple and powerful tool for ranking genetic variants. PeerJ. 2015;3:e796. https://doi.org/10.7717/peerj.796 .
doi: 10.7717/peerj.796
pubmed: 25780760
pmcid: 4358652
1000 Genomes Project Consortium; Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526: 68–74. doi: https://doi.org/10.1038/nature15393 .
Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;7809:434–43. https://doi.org/10.1038/s41586-020-2308-7 .
doi: 10.1038/s41586-020-2308-7
Sim NL, Kumar P, Hu J, Henikoff S, Schneider G, Ng PC. SIFT web server: predicting effects of amino acid substitutions on proteins. Nucleic Acids Res. 2012;40:W452-457. https://doi.org/10.1093/nar/gks539 .
doi: 10.1093/nar/gks539
pubmed: 22689647
pmcid: 3394338
Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2 - PubMed.. Accessed: Nov. 03, 2023. [Online]. Available: https://pubmed.ncbi.nlm.nih.gov/23315928/
Reva B, Antipin Y, Sander C. Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res. 2011;39:e118. https://doi.org/10.1093/nar/gkr407 .
doi: 10.1093/nar/gkr407
pubmed: 21727090
pmcid: 3177186
Shapiro MB, Senapathy P. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res. 1987;15:7155–74. https://doi.org/10.1093/nar/15.17.7155 .
doi: 10.1093/nar/15.17.7155
pubmed: 3658675
pmcid: 306199
Yeo G, Burge CB. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J Comput Biol. 2004;11:377–94. https://doi.org/10.1089/1066527041410418 .
doi: 10.1089/1066527041410418
pubmed: 15285897
Reese MG, Eeckman FH, Kulp D, Haussler D. Improved splice site detection in Genie. J Comput Biol. 1997;4:311–23. https://doi.org/10.1089/cmb.1997.4.311 .
doi: 10.1089/cmb.1997.4.311
pubmed: 9278062
Backenroth D, Homsy J, Murillo LR, Glessner J, Lin E, Brueckner M, et al. CANOES: detecting rare copy number variants from whole exome sequencing data. Nucleic Acids Res. 2014;42:e97. https://doi.org/10.1093/nar/gku345 .
doi: 10.1093/nar/gku345
pubmed: 24771342
pmcid: 4081054
Geoffroy V, Herenger Y, Kress A, Stoetzel C, Piton A, Dollfus H, et al. AnnotSV: an integrated tool for structural variations annotation. Bioinformatics. 2018;34:3572–4. https://doi.org/10.1093/bioinformatics/bty304 .
doi: 10.1093/bioinformatics/bty304
pubmed: 29669011
Brandt T, Sack LM, Arjona D, Tan D, Mei H, Cui H, et al. Adapting ACMG/AMP sequence variant classification guidelines for single-gene copy number variants. Genet Med. 2020;22:336–44. https://doi.org/10.1038/s41436-019-0655-2 .
doi: 10.1038/s41436-019-0655-2
pubmed: 31534211
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. 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. Genet Med. 2015;17:405–24. https://doi.org/10.1038/gim.2015.30 .
doi: 10.1038/gim.2015.30
pubmed: 25741868
pmcid: 4544753
Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Tissue-based map of the human proteome. Science. 2015;347:1260419. doi: https://doi.org/10.1126/science.1260419 .
Matthijs G, Souche E, Alders M, Corveleyn A, Eck S, Feenstra I, et al. Guidelines for diagnostic next-generation sequencing. Eur J Hum Genet. 2016;24:2–5. https://doi.org/10.1038/ejhg.2015.226 .
doi: 10.1038/ejhg.2015.226
pubmed: 26508566
Houston BJ, Riera-Escamilla A, Wyrwoll MJ, Salas-Huetos A, Xavier MJ, Nagirnaja L, et al. A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships. Hum Reprod Update. 2021;28:15–29. https://doi.org/10.1093/humupd/dmab030 .
doi: 10.1093/humupd/dmab030
pubmed: 34498060
pmcid: 8730311
Volozonoka L, Miskova A, Kornejeva L, Kempa I, Bargatina V, Gailite L. A systematic review and standardized clinical validity assessment of genes involved in female reproductive failure. Reproduction. 2022;163:351–63. https://doi.org/10.1530/REP-21-0486 .
doi: 10.1530/REP-21-0486
pubmed: 35451369
pmcid: 9066658
Van Der Kelen A, Okutman Ö, Javey E, Serdarogullari M, Janssens C, Ghosh MS, et al. A systematic review and evidence assessment of monogenic gene-disease relationships in human female infertility and differences in sex development. Hum Reprod Update. 2023;29:218–32. https://doi.org/10.1093/humupd/dmac044 .
doi: 10.1093/humupd/dmac044
pubmed: 36571510
Smith ED, Radtke K, Rossi M, Shinde DN, Darabi S, El-Khechen D, et al. Classification of genes: standardized clinical validity assessment of gene-disease associations aids diagnostic exome analysis and reclassifications. Hum Mutat. 2017;38:600–8. https://doi.org/10.1002/humu.23183 .
doi: 10.1002/humu.23183
pubmed: 28106320
pmcid: 5655771
Desai S, Wood-Trageser M, Matic J, Chipkin J, Jiang H, Bachelot A, et al. MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency. J Clin Endocrinol Metab. 2017;102:576–82. https://doi.org/10.1210/jc.2016-2565 .
doi: 10.1210/jc.2016-2565
pubmed: 27802094
Zhao M, Feng F, Chu C, Yue W, Li L. A novel EIF4ENIF1 mutation associated with a diminished ovarian reserve and premature ovarian insufficiency identified by whole-exome sequencing. J Ovarian Res. 2019;12:119. https://doi.org/10.1186/s13048-019-0595-0 .
doi: 10.1186/s13048-019-0595-0
pubmed: 31810472
pmcid: 6896303
Schilit SLP, Menon S, Friedrich C, Kammin T, Wilch E, Hanscom C, et al. SYCP2 translocation-mediated dysregulation and frameshift variants cause human male infertility. Am J Hum Genet. 2020;106:41–57. https://doi.org/10.1016/j.ajhg.2019.11.013 .
doi: 10.1016/j.ajhg.2019.11.013
pubmed: 31866047
Xu J, Sun Y, Zhang Y, Ou N, Bai H, Zhao J, et al. A homozygous frameshift variant in SYCP2 caused meiotic arrest and non-obstructive azoospermia. Clin Genet. 2023;104:577–81. https://doi.org/10.1111/cge.14392 .
doi: 10.1111/cge.14392
pubmed: 37337432
Okutman O, Muller J, Skory V, Garnier JM, Gaucherot A, Baert Y, et al. A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family. J Assist Reprod Genet. 2017;34:683–94. https://doi.org/10.1007/s10815-017-0900-z .
doi: 10.1007/s10815-017-0900-z
pubmed: 28401488
pmcid: 5427651
Redin C, Gérard B, Lauer J, Herenger Y, Muller J, Quartier A, et al. Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. J Med Genet. 2014;51:724–36. https://doi.org/10.1136/jmedgenet-2014-102554 .
doi: 10.1136/jmedgenet-2014-102554
pubmed: 25167861
Koscinski I, ElInati E, Fossard C, Redin C, Muller J, Velez de la Calle J et al. DPY19L2 deletion as a major cause of globozoospermia. Am J Hum Genet. 2011;88(3):344–350. doi: https://doi.org/10.1016/j.ajhg.2011.01.018 .
Dam AH, Koscinski I, Kremer JA, Moutou C, Jaeger AS, Oudakker AR, et al. Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia. Am J Hum Genet. 2007;81:813–20. https://doi.org/10.1086/521314 .
doi: 10.1086/521314
pubmed: 17847006
pmcid: 2227931
Dieterich K, Soto Rifo R, Faure AK, Hennebicq S, Ben Amar B, Zahi M, et al. Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nat Genet. 2007;39:661–5. https://doi.org/10.1038/ng2027 .
doi: 10.1038/ng2027
pubmed: 17435757
Feng R, Sang Q, Kuang Y, Sun X, Yan Z, Zhang S, et al. Mutations in TUBB8 and Human Oocyte Meiotic Arrest. N Engl J Med. 2016;374:223–32. https://doi.org/10.1056/NEJMoa1510791 .
doi: 10.1056/NEJMoa1510791
pubmed: 26789871
pmcid: 4767273
Barbaux S, El Khattabi L, Ziyyat A. ZP2 heterozygous mutation in an infertile woman. Hum Genet. 2017;136:1489–91. https://doi.org/10.1007/s00439-017-1844-1 .
doi: 10.1007/s00439-017-1844-1
pubmed: 28971300
Chen T, Bian Y, Liu X, Zhao S, Wu K, Yan L, et al. A recurrent missense mutation in ZP3 causes empty follicle syndrome and female infertility. Am J Hum Genet. 2017;101:459–65. https://doi.org/10.1016/j.ajhg.2017.08.001 .
doi: 10.1016/j.ajhg.2017.08.001
pubmed: 28886344
pmcid: 5590947
Huang HL, Lv C, Zhao YC, Li W, He XM, Li P, et al. Mutant ZP1 in familial infertility. N Engl J Med. 2014;370:1220–6. https://doi.org/10.1056/NEJMoa1308851 .
doi: 10.1056/NEJMoa1308851
pubmed: 24670168
pmcid: 4076492
Verpoest W, Okutman Ö, Van Der Kelen A, Sermon K, Viville S. Genetics of infertility: a paradigm shift for medically assisted reproduction. Hum Reprod. 2023;38:2289–95. https://doi.org/10.1093/humrep/dead199 .
doi: 10.1093/humrep/dead199
pubmed: 37801292