The translocation of the testis-determining factor, the SRY gene, from the Y to the X chromosome is a rare event that causes abnormalities in gonadal development. In all cases of males and females carrying this translocation, disorder of sex development is reported. In our study, we described a peculiar pedigree with the first evidence of four healthy females from three generations who are carriers of the newly identified t(X;Y)(q28;p11.2)(SRY+) translocation with no evidence of ambiguous genitalia or other SRY-dependent alterations. Our study was a consequence of a Non-Invasive Prenatal Test (NIPT) showing a sexual chromosomal abnormality (XXY) followed by a chorionic villus analysis suggesting a normal karyotype 46,XX and t(X;Y) translocation detected by FISH. Here, we (i) demonstrated the inheritance of the translocation in the maternal lineage via karyotyping and FISH analysis; (ii) characterised the structural rearrangement via chromosomal microarray; and (iii) demonstrated, via Click-iT^® EdU Imaging assay, that there was an absolute preferential inactivation of the der(X) chromosome responsible for the lack of SRY expression. Overall, our study provides valuable genetic and molecular information that may lead personal and medical decisions.

We report a case of a woman with a cryptic balanced translocation between chromosomes 5 and 17, suspected during genetic counseling. The woman had a history of previous fetal losses attributed to lissencephaly and intra uterine growth retardation (IUGR) and a daughter with dysmorphic features and mental retardation, previously attributed to a small deletion 5pter, detected years ago by a first generation CGH-array. This peculiar combination of personal and family history suggested the opportunity to carry out a FISH approach, focusing on chromosomes 5 and 17, based on the idea that a malsegregation secondary to a balanced translocation, might have escaped the first CGH array. This approach allowed the identification of a balanced translocation in the mother, FISH in the affected child confirmed the partial 5p deletion predicted by the previous CGH array and identified a new 17p duplication that had not been detected before. The described translocation opens the possibility of alternative imbalances that were probably responsible for previous fetal losses. The imbalances were confirmed by a new high resolution SNP array. We conclude that despite the availability of highly effective and sensitive genomic approaches a careful evaluation of medical history is highly recommended since it can suggest clinical hypothesis that can be confirmed by more classical and molecular cytogenetic based approaches.

Gynecomastia in adolescence is a benign condition that mostly disappears spontaneously within approximately two years from onset. When it is associated with hypogonadism, it may suggest a disorder of sexual differentiation. We report the case of a young man (18 years old) with gynecomastia associated with azoospermia, small testes, hyperestrogenism and hypergonadotropic hypogonadism. A karyotype 46,XX was found, and searching for SRY (sex-determining region Y) by fluorescence in situ hybridization (FISH) highlighted the presence of the gene on the terminal region of the short arm, with breakpoints likely in Xp22.3 and Yp11.3. Implications of testosterone replacement therapy with respect to sex differentiation disorder and to physical performance are discussed.