46,XX males with SRY gene translocation: cytogenetics and molecular characterization

Abstract

Abstract Purpose XX male syndrome also known as De la Chapelle syndrome/Testicular Disorder of Sex Development (DSD) is a rare genetic abnormality, identified by a partial or complete mismatch between phenotypic and genotypic gender of an individual. The present study describes the pertinent clinical, biochemical, cytogenetics, and molecular findings in four phenotypically normal males, presented with gonadal dysgenesis and hypergonadotrophic hypogonadism. Method Clinical characteristics and biochemical parameters in four patients were assessed. Further, chromosomal analysis has been performed using conventional karyotyping. FISH and Y chromosome microdeletion assays were carried out to confirm the presence of male-specific genes followed by microarray analysis. Result Chromosomal analysis revealed a 46,XX karyotype, FISH showed the presence of 2 normal X chromosomes along with translocation of the SRY gene on the short (p) arm of one of the X chromosome. Molecular analysis for Y chromosome microdeletion revealed the presence of the SRY gene with a complete absence of azoospermic factor regions (AZFa, AZFb, and AZFc) on the long (q) arm of the Y chromosome. Chromosomal microarray revealed no significant copy number variation. Conclusions The peculiar translocation of the SRY gene in 46,XX males strongly supports the inclusion of cytogenetic testing for establishing diagnosis and genetic counseling for infertility and/or hormonal imbalances in individuals. The present study provides insight into the cascade of events triggered by the SRY gene in the XX genome, which reinforces the differentiation towards the formation of testes while actively inhibiting ovarian development.