Testis development in the absence of SRY: chromosomal rearrangements at SOX9 and SOX3
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Vetro, Annalisa
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Dehghani, Mohammad Reza
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Kraoua, Lilia
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Giorda, Roberto
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Beri, Silvana
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Cardarelli, Laura
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Merico, Maurizio
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Manolakos, Emmanouil
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Parada Bustamante, Alexis
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Castro, Andrea
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Radi, Orietta
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Camerino, Giovanna
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Brusco, Alfredo
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Sabaghian, Marjan
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Sofocleous, Crystalena
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Forzano, Francesca
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Palumbo, Pietro
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Palumbo, Orazio
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Calvano, Savino
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Zelante, Leopoldo
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Grammatico, Paola
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Giglio, Sabrina
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Basly, Mohamed
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Chaabouni, Myriam
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Carella, Massimo
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Russo, Gianni
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Bonaglia, Maria Clara
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Zuffardi, Orsetta
Admission date
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2015-11-10T20:30:41Z
Available date
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2015-11-10T20:30:41Z
Publication date
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2015
Cita de ítem
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European Journal of Human Genetics Volumen: 23 Número: 8 Páginas: 1025-1032 Aug 2015
en_US
Identifier
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DOI: 10.1038/ejhg.2014.237
Identifier
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https://repositorio.uchile.cl/handle/2250/134995
General note
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Artículo de publicación ISI
en_US
Abstract
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Duplications in the similar to 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 similar to 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 similar to 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 similar to 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.