A Novel Balanced Chromosomal Translocation in an Azoospermic Male: A Case Report

Abstract

Background: Balanced translocation and azoospermia as two main reasons for recurrent pregnancy loss are known to be the leading causes of infertility across the world. Balanced translocations in azoospermic males are very rare and extensive studies need to be performed to elucidate the translocation status of the affected individuals.

Case presentaion: The cytogenetic characterization of a 28 year old male and his female partner is reported in this study. The male partner was diagnosed with non-obstructive azoospermia (NOA) and the couple was unable to conceive. Cytogenetic analysis by karyotyping through Giemsa-trypsin-giemsa banding technique (GTG) showed a novel balanced translocation, 46,XY,t(19;22)(19q13.4;22q11.2), 13ps+ in the male and the female karyotype was found to be 46,XX. Multicolor fluorescence in situ hybridization (mFISH) analysis on paternal chromosomal preparations confirmed both the region and origin of balanced translocation. The status of Y chromosome microdeletion (YMD) was analyzed and no notable microdeletion was observed. Furthermore, protein-protein interaction (PPI) network analysis was performed for breakpoint regions to explore the possible functional genetic associations.

Conclusion: The azoospermic condition of the male patient along with novel balanced chromosomal translocation was responsible for infertility irrespective of its YMD status. Therefore, cytogenetic screening of azoospermic patients should be performed in addition to routine semen analysis to rule out or to confirm presence of any numerical or structural anomaly in the patient.

Keywords: Azoospermia; Balanced translocation; Infertility; Multicolor fluorescence in situ hybridization.

Figure 1.

Pedigree analysis: Pedigree analysis of the proband up to previous three generations. White symbol (Square or circle)-a healthy person, white symbol (Square or circle with diagonal stroke)-death of that individual, individuals connected with double line–involved in consanguineous marriage, downward line with a single line–no issues, downward line with a double line–individual with infertility

Figure 2.

Karyotype analysis: GTG-banded chromosomal analysis of the proband, which reveals the presence of a balanced translocation involving chromosome 19 and 22 along with chromosome 13 ps+.

Figure 3.

Multicolor fluorescence in situ hybridization (mFISH): A stable balanced chromosomal translocation in the proband, detected by mFISH. Chromosomes involved in this translocation are indicated by arrows; a balanced chromosomal translocation is shown involving two chromosomes 19 and 22

Figure 4.

Y chromosome microdeletion study: 1.5% agarose gel image of the specimen for Y chromosome microdeletion analysis by PCR. Two different loci for AZFa, AZFb and AZFc along with SRY and ZFY (Control) were used for analysis along with a positive control for AZFa microdeletion. Lane 1 and 7: DNA ladder (250 bp plus) Lane 2: Positive control for YMD (AZFa loci-SY86–318 bp) Lane 3: PCR product for ZFY(495 bp) and SY86 (318 bp) [AZFa locus] Lane 4: PCR product for SRY (472 bp) and SY134 (301 bp) [AZFb locus] Lane 5: PCR product for SY254 (380 bp) [AZFc locus] and SY127 (274 bp) [AZFb] Lane 6: PCR product for SY84 (326 bp) [AZFa locus] and SY255 (123 bp) [AZFc locus] Lane 8: No template control

Figure 5.

Breakpoint analysis through protein-protein interaction studies. A) STRING generated PPI networks between all the proteins present at the breakpoint location; B) PPI networks between the selected proteins involved in the breakpoint region, which has basic cellular functions