A comparative genomic hybridization study in a 46,XX male

Area of Science:

• Genetics and Molecular Biology
• Human Reproduction and Infertility
• Cytogenetics

Background:

• XX males are a rare genetic condition characterized by male phenotype and an XX karyotype.
• The presence of Y chromosome material, particularly the SRY gene, is crucial for male sex determination in these individuals.
• Conventional cytogenetic methods may not detect subtle Y chromosome translocations in XX males.

Observation:

• A 33-year-old azoospermic male with an XX karyotype presented with infertility.
• Fluorescence in situ hybridization (FISH) revealed Y chromosome sequences on the short arm of an X chromosome.
• Polymerase chain reaction (PCR) confirmed the presence of the SRY gene and amelogenin gene on the X chromosome.

Findings:

• FISH analysis detected Y chromosome material on the X chromosome, not visible with standard G-banding.
• PCR confirmed the presence of the SRY gene and the amelogenin gene (AMGX) in the pseudoautosomal region of the X chromosome.
• Comparative genomic hybridization (CGH) identified the Y chromosome region Yp11.2-pter and confirmed two normal X chromosomes.

Implications:

• This case highlights the utility of advanced genetic techniques like FISH, PCR, and CGH in diagnosing XX males.
• The findings underscore the importance of identifying Y chromosome material, especially the SRY gene, for understanding male development in XX individuals.
• Further research using CGH and PCR is recommended to characterize the clinical variability in XX males, considering genes beyond the Y chromosome.