A Rare Case of 45,X/46,X,del(Y)(q12→qter) Mosaicism in An Infertile Male with Y Chromosome Microdeletion

Abstract

Background: Males with 45,X/46,XY karyotype have two different types of cells. This condition is associated with a wide range of clinical phenotypes. In infertile males, the mosaic 45,X/46,XY karyotype is a frequent sex chromosome defect and they might be able to conceive with the help of assisted reproductive technology; nevertheless, there is a potential risk of transmission of azoospermia factor (AZF) microdeletions in addition to 45,X to all the male progeny. In this case report, the purpose was to present a rare sex chromosomal mosaicism of an infertile man.

Case presentation: Comprehensive molecular and cytogenetic analysis of an infertile male was performed in this case study. A 27-year-old male was presented with history of azoospermia and was unable to conceive after being involved in five years of marriage. Cytogenetic investigation revealed a rare mosaic karyotype pattern of 45,X/46,X,del(Y)(q12→qter). Y chromosome microdeletion (YMD) analysis revealed notable deletions of 06 loci. Comparative genomic hybridization (CGH) microarray was performed to investigate probable functional genetic associations.

Conclusion: Deletion of Y-linked genes leads to different testicular pathological conditions contributing to male infertility. Individuals with normal male phenotype harbor YMD, although size and location of the deletion do not always correspond well with quality of sperm. Therefore, in addition to semen analysis, identification of genetic variables is important which will play a crucial role in proper diagnosis and management of infertile couples. The present case study demonstrates the significance of comprehensive molecular testing and cytogenetic screening for individuals with idiopathic infertility.

Keywords: Azoospermia factor (AZF); Chromosomal microarray analysis (CMA); Comparative genomic hybridization (CGH); Fluorescence in situ hybridization (FISH); Infertility; Y-chromosome microdeletion (YMD).

Figure 1.

Image of karyotype analysis indicating loss of chromosome Y (left) along with partial deletion of Y chromosome (right)

Figure 2.

Fluorescence in-situ hybridization: Image A, showing loss of chromosome Y(XO) and image B is showing presence of both sex chromosomes (XY)

Figure 3.

Agarose gel (1.8%) image of Y chromosome microdeletion analysis by multiplex PCR Lane 1: DNA ladder (100 bp). Lane 2: Negative control for ZFY-495 bp, SY84 (326 bp) [AZFa locus], SY134 (301 bp) [AZFb locus], SY127 (274 bp) [AZFb locus]. Lane 3: Negative control for SRY–472 bp, SY254 (400 bp) [AZFc locus], SY86 (320 bp) [AZFa locus], SY255 (126 bp) [AZFc locus] Lane 4: Test sample; two bands indicating presence of ZFY-495 bp, SY84 (326 bp) [AZFa locus], and absence of two bands indicating deletion of SY134 (301 bp) [AZFb locus], SY127 (274 bp) [AZFb locus]. Lane 5: Test sample; two bands indicating presence of SRY–472 bp, SY86 (320 bp) [AZFa locus], and absence of two bands indicating deletion of SY254 (400 bp), and SY255 (126 bp) [AZFc locus]. Lane 6: No template control; no bands indicating absence of any kind of nucleic acid contamination

Figure 4.

Agarose gel (1.8%) image of Y chromosome microdeletion (AZFc region specific) analysis by multiplex PCR Lane 1: Test sample; absence of four bands indicating deletion of SY254 (400 bp), SY160 (236 bp), SY145 (143 bp), and SY 255 (126 bp) [AZFc locus]. Lane 2: DNA ladder (100 bp). Lane 3: Negative control; presence of four bands indicating no deletion of SY254 (400 bp), SY160 (236 bp), SY145 (143 bp), and SY 255 (126 bp) [AZFc locus]. Lane 4: Test sample; absence of four bands indicating deletion of SY254 (400 bp), SY160 (236 bp), SY145 (143 bp), and SY 255 (126 bp) [AZFc locus]. Lane 5: No template control; no bands indicating absence of any kind of nucleic acid contamination

Figure 5.

A representative genome view of array CGH data of the test sample