Karyotype determination and reproductive guidance for short stature women with a hidden Y chromosome fragment

Two unrelated couples came to the Reproductive and Genetic Hospital of Citic-Xiangya to ask for reproductive guidance. One couple had an affected son and the other couple had secondary infertility. Conventional GTG banding showed that the women in both couples had a 46,X,add(X)(p22) karyotype. Further molecular cytogenetic studies showed that both women had a 46,X,der(X)t(X;Y)(p22;q11.2) karyotype and that the affected boy had inherited the derivative X chromosome, which resulted in an Xp contiguous gene syndrome. After an assessment of reproductive risk, the first couple conceived naturally and opted for prenatal diagnosis (PND) by amniocentesis. No abnormal karyotypes were found for the twin pregnancy and healthy twin girls were born after a full-term normal pregnancy. The second couple chose to undergo IVF with preimplantation genetic diagnosis (PGD). Two PGD cycles were performed by fluorescence in-situ hybridization. In the first PGD cycle, all three embryos had abnormal hybridization signals. In the second cycle, a male embryo with normal hybridization signals was transferred into the womb and a normal pregnancy was achieved. The results show the importance of detecting the derivative chromosome followed by PND or PGD if a woman carries an Xp;Yq translocation.Two unrelated couples came to our clinic to ask for reproductive guidance. The first couple had an affected son. Conventional GTG banding showed the woman carried a derivative metacentric X chromosome. Further molecular cytogenetic study identified this derivative X chromosome originated from a cryptic translocation between Xp and Yq and the karyotype of the woman was determined as 46,X,der(X)t(X;Y)(p22;q11.2), and the affected boy had inherited the derivative X chromosome, which resulted in an Xp contiguous gene syndrome. After assessment of reproductive risk, the couple conceived naturally. Prenatal diagnosis by amniocentesis showed a normal karyotype for the twin pregnancy and healthy twin girls were born at full term. The other couple was affected by secondary infertility. They chose to undergo IVF with preimplantation genetic diagnosis (PGD). Two PGD cycles was performed by fluorescence in-situ hybridization. In the second cycle, a male embryo with normal hybridization signals was transferred to the womb and a normal pregnancy was achieved. We emphasize the importance of identifying the hidden Y chromosome fragment to avoid the delivery of unbalanced offspring among women with a normal phenotype apart from short stature. This is the first report of the application of PGD for this unbalanced translocation 46,X,der(X)t(X;Y)(p22;q11.2).