Background: The effects of a balanced X; Autosome translocation [t(X;A)] on the fertility of carrier females led to the definition of the Xq13-->q27 region as critical for ovarian function and reproductive lifespan. We describe here a teenager with ovarian failure likely due to a balanced t(X;17)(q22;q25).
Case: The 16 year-old patient presented with secondary amenorrhea. She exhibited height of 164 cm, slender habitus, and sexual development Tanner 2.
Methods: Hormonal determinations, GTG- and RBG-banded karyotypes, fluorescence in situ hybridization, and human androgen receptor assay.
Results: FSH of 141 mIU/ml and LH of 46 mIU/ml); karyotype 46,X,t(X;17)(q22;q25)[30].ish der(X)t(X;1 7)(17qsubt el+); skewed inactivation of the normal X which was the maternal one as shown by the HUMARA assay. The maternal chromosomes were 46,XX; the father was unavailable.
Conclusions: The patient's (X;17) translocation likely accounts for her ovarian failure via an epigenetic downregulation of ovary expressed 17q25 genes relocated next to the Xq21 POF Critical Region 1 and related to ovarian development and function. Her otherwise inconspicuous phenotype agrees with the preferential inactivation of the normal X-chromosome that preserves the gene homeostasis in women with a balanced t(X;A). Finally, the normal maternal karyotype along with the HUMARA results and the sterility of males carrying a t(X;A) strongly suggests that this t(X;17) was a paternal de novo mutation.