Abstract
BackgroundA rare disease is that an individual with a non-chimeric karyotype of 45, X develops into a male. We explored the genetic aetiology of an infertility male with an apparent 45, X karyotype, which was subsequently verified as cryptic translocation between chromosomes Y and 15. MethodsPeripheral blood sample was collected from the patient and subjected to a range of genetic testing, including conventional chromosomal karyotyping, short tandem repeat (STR) analysis for azoospermia factor (AZF) region, fluorescence in situ hybridization (FISH) with specific probes for CSP X/CSP Y, CSP Y/D15Z1/PML and SRY/D15Z1/PML, and chromosomal microarray analysis (CMA) for genomic copy number variations (CNVs). ResultsThe patient was found to have an apparent 45,X karyotype. STR analysis showed that he possessed a short arm of the Y chromosome, including the SRY gene but the absence of a long arm of the Y chromosome, including AZFa+b+c and Yqter. A FISH assay using CSP X and CSP Y probes showed a green signal at the centromere of the X chromosome and a red signal for the Y centromeric sequence on a D-group-sized chromosome. By FISH assaying with D15Z1 and CSP Y probes, chromosomes 15 and Y centromeric signals appeared closely on a single chromosome, as ascertained by the PML control probe. A further FISH assay with D15Z1 and SRY probes revealed a signal of the SRY gene at the end of one arm of chromosome 15. The result of the CMA indicated a deletion with an approximate size of 45.31 Mb spanning from Yq11 to Yter. ConclusionAlthough the 45,X male patient did not harbour an intact Y chromosome, his genome contained the SRY gene derived from the translocation of the Yp, which probably triggered the male differentiation and development. Imbalanced translocations of Yp to other chromosomes can result in short stature and infertility among patients. Delineation of the genetic aetiology can guide early intervention and assisted reproduction in adulthood.
