Critical role of Yp inversion in PRKX/PRKY-mediated Xp;Yp translocation in a patient with 45,X testicular disorder of sex development.

45,X testicular disorder of sex development (TDSD), previously known as 45,X maleness, with unbalanced Xp;Yp translocation is an extremely rare condition caused by concomitant occurrence of loss of an X chromosome of maternal origin and an aberrant Xp;Yp translocation during paternal meiosis. We identified a Japanese male infant with an apparently 45,X karyotype who exhibited chondrodysplasia punctata and growth failure. Cytogenetic analysis revealed a 45,X.ish der(X)t(X;Y)(p22.33;p11.2)(DXZ1+,SRY+) karyotype. Array comparative genome hybridization analysis showed a simple Xp terminal deletion involving SHOX and ARSE with the breakpoint just centromeric to PRKX, and an apparently complex Yp translocation with the middle Yp breakpoint just telomeric to PRKY and the centromeric and the telomeric Yp breakpoints around the long inverted repeats for the generation of a common paracentric Yp inversion. Subsequently, a long PCR product was obtained with an X-specific and a Y-specific primers that were designed on the assumption of the presence of a Yp inversion that permits the alignment of PRKX and PRKY in the same direction, and the translocation fusion point was determined to reside within a 246 bp X-Y homologous segment at the "hot spot A" in the 5' region of PRKX/PRKY, by sequential direct sequencing for the long PCR product. These results argue not only for the presence of rare 45,X-TDSD with Xp;Yp translocation, but also for a critical role of a common paracentric Yp inversion in the occurrence of PRKX/PRKY-mediated unbalanced Xp;Yp translocation.