Nonmosaic Isodicentric Y Chromosome: A Rare Cause of Azoospermia- From Genetics to Clinical Practice

Abstract

Azoospermia is diagnosed when no spermatozoa can be detected after centrifugation of seminal fluid on at least two separate occasions. A number of genetic disorders can be related to nonobstructive azoospermia, and in up to 15% of azoospermic males, a genetic disorder is diagnosed. A 36-year-old male with nonobstructive azoospermia was referred to our department of diabetes and endocrinology due to an aberrant testicular biopsy. The biopsy showed a disrupted spermatogenesis with a maturation arrest at the spermatocyte level in most tubuli seminiferi while others showed a Sertoli cell-only syndrome. Screening for Y chromosome microdeletions on peripheral blood using molecular analysis detected a terminal deletion of AZFbc. The result of karyotyping and fluorescence in situ hybridization (FISH) described an isodicentric Y chromosome with karyotype 46,X,idic(Y)(q11.22). Based on this case and the current available literature, we conclude that performing a testicular biopsy in patients with a nonmosaic idic(Y)(q) is not meaningful and that the prognosis on infertility is poor. Biological fatherhood is extremely unlikely in these patients, and proper counselling should be provided.

Figure 1

Testicular biopsy with maturation arrest at the spermatocyte level. Red arrow = spermatocyte. Blue arrow = spermatogona. Yellow arrow = Sertoli cell.

Figure 2

Karyotyping and fluorescence in situ hybridization (FISH) analyses. (a) Conventional chromosome analysis of cultured peripheral lymphocytes identified an idic(Y)(q11.22) chromosome. (b) FISH analysis was performed using probes for the telomeric regions of both the X and Y chromosomes. Green signals indicate the pter-region of the X and Y chromosomes (Abbott TelVysion Xp/Yp probe). Red signals indicate the qter-region of the X and Y chromosomes (in-house subtelomeric XqYq probe). FISH analysis demonstrated that the aberrant Y chromosome contained 2 signals for the Yp subtelomeric probe and absence of the Yq subtelomeric probe. This confirmed the presence of an idic(Y)(q).

Figure 3

Schematic representation of aberrant homologous crossing over between opposite arms of a palindrome during spermatogenesis with the formation of an isodicentric Y chromosome.

Figure 4

Schematic representation of isodicentric Y chromosome idic(Y)(q11.22). The breakpoint (arrow) is located at q11.22 (long arm), with a duplication of short arm, centromere, and proximal long arm and loss of all distal long arm material.