Testis development in the absence of SRY: Chromosomal rearrangements at SOX9 and SOX3

Annalisa Vetro, Mohammad Reza Dehghani, Lilia Kraoua, Roberto Giorda, Silvana Beri, Laura Cardarelli, Maurizio Merico, Emmanouil Manolakos, Alexis Parada-Bustamante, Andrea Castro, Orietta Radi, Giovanna Camerino, Alfredo Brusco, Marjan Sabaghian, Crystalena Sofocleous, Francesca Forzano, Pietro Palumbo, Orazio Palumbo, Savino Calvano, Leopoldo ZelantePaola Grammatico, Sabrina Giglio, Mohamed Basly, Myriam Chaabouni, Massimo Carella, Gianni Russo, Maria Clara Bonaglia, Orsetta Zuffardi

Research output: Contribution to journalArticlepeer-review


Duplications in the ∼2 Mb desert region upstream of SOX9 at 17q24.3 may result in familial 46,XX disorders of sex development (DSD) without any effects on the XY background. A balanced translocation with its breakpoint falling within the same region has also been described in one XX DSD subject. We analyzed, by conventional and molecular cytogenetics, 19 novel SRY-negative unrelated 46,XX subjects both familial and sporadic, with isolated DSD. One of them had a de novo reciprocal t(11;17) translocation. Two cases carried partially overlapping 17q24.3 duplications ∼500 kb upstream of SOX9, both inherited from their normal fathers. Breakpoints cloning showed that both duplications were in tandem, whereas the 17q in the reciprocal translocation was broken at ∼800 kb upstream of SOX9, which is not only close to a previously described 46,XX DSD translocation, but also to translocations without any effects on the gonadal development. A further XX male, ascertained because of intellectual disability, carried a de novo cryptic duplication at Xq27.1, involving SOX3. CNVs involving SOX3 or its flanking regions have been reported in four XX DSD subjects. Collectively in our cohort of 19 novel cases of SRY-negative 46,XX DSD, the duplications upstream of SOX9 account for ∼10.5% of the cases, and are responsible for the disease phenotype, even when inherited from a normal father. Translocations interrupting this region may also affect the gonadal development, possibly depending on the chromatin context of the recipient chromosome. SOX3 duplications may substitute SRY in some XX subjects.

Original languageEnglish
Pages (from-to)1025-1032
Number of pages8
JournalEuropean Journal of Human Genetics
Issue number8
Publication statusPublished - Aug 21 2015

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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