Journal article
Authors list: Riera-Escamilla, Antoni; Vockel, Matthias; Nagirnaja, Liina; Xavier, Miguel J.; Carbonell, Albert; Moreno-Mendoza, Daniel; Pybus, Marc; Farnetani, Ginevra; Rosta, Viktoria; Cioppi, Francesca; Friedrich, Corinna; Oud, Manon S.; van der Heijden, Godfried W.; Soave, Armin; Diemer, Thorsten; Ars, Elisabet; Sanchez-Curbelo, Josvany; Kliesch, Sabine; O'Bryan, Moira K.; Ruiz-Castane, Eduard; Azorin, Fernando; Veltman, Joris A.; Aston, Kenneth, I; Conrad, Donald F.; Tuettelmann, Frank; Krausz, Csilla
Publication year: 2022
Pages: 1458-1471
Journal: American Journal of Human Genetics
Volume number: 109
Issue number: 8
ISSN: 0002-9297
eISSN: 1537-6605
Open access status: Green
DOI Link: https://doi.org/10.1016/j.ajhg.2022.06.007
Publisher: Cell Press
Abstract:
Although the evolutionary history of the X chromosome indicates its specialization in male fitness, its role in spermatogenesis has largely been unexplored. Currently only three X chromosome genes are considered of moderate-definitive diagnostic value. We aimed to provide a comprehensive analysis of all X chromosome-linked protein-coding genes in 2,354 azoospermic/cryptozoospermic men from four independent cohorts. Genomic data were analyzed and compared with data in normozoospermic control individuals and gnomAD. While updating the clinical significance of known genes, we propose 21 recurrently mutated genes strongly associated with and 34 moderately associated with azoospermia/cryptozoospermia not previously linked to male infertility (novel). The most frequently affected prioritized gene, RBBP7, was found mutated in ten men across all cohorts, and our functional studies in Drosophila support its role in germ stem cell maintenance. Collectively, our study represents a significant step towards the definition of the missing genetic etiology in idiopathic severe spermatogenic failure and significantly reduces the knowledge gap of X-linked genetic causes of azoospermia/cryptozoospermia contributing to the development of future diagnostic gene panels.
Citation Styles
Harvard Citation style: Riera-Escamilla, A., Vockel, M., Nagirnaja, L., Xavier, M., Carbonell, A., Moreno-Mendoza, D., et al. (2022) Large-scale analyses of the X chromosome in 2,354 infertile men discover recurrently affected genes associated with spermatogenic failure, American Journal of Human Genetics, 109(8), pp. 1458-1471. https://doi.org/10.1016/j.ajhg.2022.06.007
APA Citation style: Riera-Escamilla, A., Vockel, M., Nagirnaja, L., Xavier, M., Carbonell, A., Moreno-Mendoza, D., Pybus, M., Farnetani, G., Rosta, V., Cioppi, F., Friedrich, C., Oud, M., van der Heijden, G., Soave, A., Diemer, T., Ars, E., Sanchez-Curbelo, J., Kliesch, S., O'Bryan, M., ...Krausz, C. (2022). Large-scale analyses of the X chromosome in 2,354 infertile men discover recurrently affected genes associated with spermatogenic failure. American Journal of Human Genetics. 109(8), 1458-1471. https://doi.org/10.1016/j.ajhg.2022.06.007
Keywords
DBIGH1; HUMAN FATE; MALE GERMLINE
