Copy-number analysis of Y-linked loci in young men with non-obstructive azoospermia: Implications for the rarity of early onset mosaic loss of chromosome Y

Erina Suzuki; Yoshitomo Kobori; Momori Katsumi; Kikumi Ushijima; Toru Uchiyama; Hiroshi Okada; Mami Miyado; Maki Fukami

doi:10.1002/rmb2.12321

Copy-number analysis of Y-linked loci in young men with non-obstructive azoospermia: Implications for the rarity of early onset mosaic loss of chromosome Y

Reprod Med Biol. 2020 Mar 2;19(2):178-181. doi: 10.1002/rmb2.12321. eCollection 2020 Apr.

Authors

Erina Suzuki¹, Yoshitomo Kobori², Momori Katsumi^{1

3}, Kikumi Ushijima¹, Toru Uchiyama⁴, Hiroshi Okada², Mami Miyado¹, Maki Fukami¹

Affiliations

¹ Department of Molecular Endocrinology National Research Institute for Child Health and Development Tokyo Japan.
² Department of Urology Dokkyo Medical University Saitama Medical Center Koshigaya Japan.
³ Department of NCCHD Child Health and Development Graduate School Tokyo Medical and Dental University Tokyo Japan.
⁴ Department of Human Genetics National Research Institute for Child Health and Development Tokyo Japan.

Abstract

Purpose: Mosaic loss of chromosome Y (mLOY) is a common feature in elderly men. If mLOY can also occur in young men, it may lead to spermatogenic failure due to loss of spermatogenic genes. Indeed, previous studies detected the 45,X/46,XY karyotype in a few young men with spermatogenic failure. The present study aimed to clarify the frequency of cryptic mLOY in reproductive-aged men with spermatogenic failure.

Methods: We studied 198 men at ages 24-55 years who presented with etiology-unknown non-obstructive azoospermia. Prior this study, these patients underwent G-banding analysis for 20 leukocytes and were found to have 46,XY karyotype. We analyzed copy numbers of chromosome Y in blood cells by using semi-quantitative multiplex PCR for AMELY/AMELX, array-based comparative genomic hybridization (CGH) for the AMELY locus, and droplet digital PCR for SRY, USP9Y, and UTY.

Results: Multiplex PCR showed borderline low AMELY/AMELX ratios in three patients. However, for the three patients, CGH excluded deletion of the AMELY locus, and droplet digital PCR suggested preserved copy numbers of all tested loci.

Conclusion: This study highlights the rarity of leukocyte mLOY in reproductive-aged men with spermatogenic failure. In addition, our data imply that standard karyotyping is sufficient to screen early onset mLOY.

Keywords: Y‐linked gene; azoospermia; chromosome deletion; karyotype; sex chromosome.