The prevalence of 45,X/46,XY mosaicisms or its variants in this male infertility study was 0.29% (19/6545) (approximately 29/10,000), which was consistent with previous studies (0.27%)[9]. However, this is much higher than its incidence (1.5/10,000) in newborns [10], indicating that 45,X/46,XY mosaicisms are common chromosomal aberrations associated with male infertility. In this study, we analysed 6545 infertile men and found that 68.42% (13/19) of patients with 45,X/46,XY mosaicism had AZF microdeletions. In previous studies, Li et al investigated 5269 cases of infertility men and found that 71.43% (10/14) of patients with 45,X/46,XY mosaicism exhibited AZF microdeletions [9]. Pan et al detected 5235 male patients with primary infertility and reported that 83.3% (5/6) patients with mosaic karyotype 45,X/46,XY had AZF deletions [11]. dos Santos AP et al studied 15 patients with mosaicism and found that approximately 40% (6/15) patients with AZF deletions had mosaic karyotype 45,X/46,XY [12].The prevalence of Y chromosome microdeletions in patients with 45,X/46,XY mosaicism or its variants was different from other reports, main cause of which might was the sample size. However, our results were consistent with previous studies that a high frequency of Y chromosome microdeletions was detected in patients with 45,X/46,XY mosaicism or its variants.
In the study, 78.95% (15/19) patients with 45,X/46,XY mosaicism had a structurally abnormal Y chromosome in the 46,XY cell line, while 21.05% (4/19) had pure 45,X/46,XY mosaicism. Different from previous studies, we found that 45,X/46,XY mosaicism in patients with Y chromosome microdeletions almost all exhibited a structurally abnormal Y chromosome. In this study, 92.31% (12/13) of 45,X/46,XY mosaicism in patients with Y chromosome microdeletions exhibited a structural Y chromosome abnormalities in 46,XY cell line. Li et al found 10 patients with 45,X/46,XY mosaicism had AZF microdeletions, and 40.00% (4/10) of them exhibited a structurally abnormal Y chromosome[9]. dos Santos AP et al reported a group of six patients with 45,X/46,XY mosaicism had AZF microdeletions, and 66.67% (4/6) of them an abnormal Y chromosome had been detected in cytogenetic analysis [12]. Pan et al reported 8 patients with mosaic karyotype 45,X/46,XY had AZF deletions, and 37.5% (3/8) of them had an structurally abnormal Y chromosome [11]. The prevalence of 45,X/46,XY mosaicism carrying a structurally abnormal Y chromosome in patients with Y chromosome microdeletions was much higher than other reports. Karyotyping is a reliable technique for the identification of most chromosomal abnormalities, but it cannot detect subtle variations in chromosomal structure, only detecting unbalanced anomalies of at least 5–20 Mb[13]. Patients with the del(Y)(q12) karyotype had a structural deletion on the Y chromosome, which is close to the AZF region. In addition, our previous study confirmed that Y chromosome microdeletions only involved Y chromosome polymorphic variants (especially Yqh- and Y ≤ 21 variants) and had no relationship with other chromosome polymorphisms[8]. There were six patients with Yqh-, five with del(Y) (q12), and one with Y ≤ 21 in the study, which might be the cause of the high frequency of structural Y chromosome abnormalities in patients with Y chromosome microdeletions. In addition, only one of 13 individuals with an apparently normal Y chromosome had AZF microdeletions in this study. This frequency (1/13) was lower than that found by Alvarez-Nava et al (3/11) [14] and lower than that found by Patsalis et al (4/7) [15]. Taken together these findings suggest that 8/31(25.81%) individuals with 45,X/46,XY and apparently normal Y chromosome may have Y microdeletions.
In the present study, the most frequent microdeletions were detected in the AZFc region, followed by the deletion of the AZFb + c region. Consistent with previous researches, we found only the deletions of AZFc region and AZFb + c region invovled the 45,X/46,XY mosaicism, and deletion of AZFb + c region might also make men more likely to lose their Y chromosomes. Several studies have found AZFc deletion to be a premutation for 45,X and for the mosaic phenotype 45,X/46,XY [16, 17]. In this study, only 0.96% of men with the AZFc deletion and 18.33% of men with the AZFb + c deletion involved 45,X/46,XY mosaicism, of which AZFb + c microdeletions and AZFc microdeletions accounted for 84.62% (11/13) and 15.38% (2/13), respectively. Hopps et al[18] reported that one out of 25 (1/25, 4.0%) men with AZFc deletion and three out of 12 (3/12, 25.0%) men with AZFb + c deletions had 45,X/46,XY mosaicism. Li et al reported that ten cases (71.43%, 10/14) of 45,X mosaicism exhibiting AZF microdeletions, including two of ten (20.0%, 2/10) with AZFc deletions and the other eight (80.0%, 8/10) with AZFb + c deletions. Aydemir et al[19] documented a rare case of 45,X/46,XY mosaicism with deletion of the AZFb + c region. Pan et al [11] reported all of five male patients (100.0%, 5/5) with a mosaic karyotype 45,X/46,XY had AZFb + c deletions. However, Kleiman SE et al [20] reported that 10.29% (7/68) men with the AZFb + c deletion and 4.76% (1/21) men with AZFb deletion was found to have the 45,X/46,XY karyotype, which was the only report about the deletions of AZFb region invovled the 45,X/46,XY mosaicism. Larger sample size and more data are needed to further prove whether AZFb microdeletion will lead to the ocure of 45,X/46,XY mosaicism.