46,X,+mar(Y) as a Rare Etiology of Non-obstructive Male Infertility.

Abstract

Marker chromosomes derived from the Y chromosome are rare and can present with either disorders of sex development (DSD) or infertility. We assessed a unique case of a 38-year-old Indian male who presented with primary infertility and azoospermia. Cytogenetic analysis demonstrated a karyotype of 46,X,+mar, and further fluorescence in situ hybridisation studies confirmed the marker to be of Y chromosomal origin. Microarray revealed an interstitial deletion of 15.7 Mb spanning Yq11.1-q11.23 with preservation of the Yp arm. Multiplex polymerase chain reaction showed complete loss of the azoospermia factor (AZF) a, AZFb and AZFc regions. Based on integrated cytogenetic and molecular findings, the final karyotype was revised to 46,X,der(Y)del(Y)(q11.1q11.23). Interestingly, the marker chromosome retained the sex-determining region Y (SRY) gene, explaining the development of a male phenotype, but the absence of the AZF loci accounted for the failure of spermatogenesis. This case highlights the importance of integrated cytogenetic and molecular approaches in evaluating unexplained male infertility and represents a rare example of SRY-positive testicular DSD associated with a Y-derived marker chromosome lacking critical spermatogenic regions.