{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:54:57Z","timestamp":1792652097763,"version":"4.5.0"},"reference-count":25,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2011,10,5]]},"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The early gonad is bipotential and can differentiate into either a testis or an ovary. In XY embryos, the\n                      <jats:italic>SRY<\/jats:italic>\n                      gene triggers testicular differentiation and subsequent male development via its action on a single gene,\n                      <jats:italic>SOX9<\/jats:italic>\n                      . The supporting cell lineage of the bipotential gonad will differentiate as testicular Sertoli cells if\n                      <jats:italic>SOX9<\/jats:italic>\n                      is expressed and conversely will differentiate as ovarian granulosa cells when\n                      <jats:italic>SOX9<\/jats:italic>\n                      expression is switched off.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Through copy number variation mapping this study identified duplications upstream of the\n                      <jats:italic>SOX9<\/jats:italic>\n                      gene in three families with an isolated 46,XX disorder of sex development (DSD) and an overlapping deletion in one family with two probands with an isolated 46,XY DSD. The region of overlap between these genomic alterations, and previously reported deletions and duplications at the\n                      <jats:italic>SOX9<\/jats:italic>\n                      locus associated with syndromic and isolated cases of 46,XX and 46,XY DSD, reveal a minimal non-coding 78\u2005kb sex determining region located in a gene desert 517\u2013595\u2005kb upstream of the\n                      <jats:italic>SOX9<\/jats:italic>\n                      promoter.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These data indicate that a non-coding regulatory region critical for gonadal SOX9 expression and subsequent normal sex development is located far upstream of the\n                      <jats:italic>SOX9<\/jats:italic>\n                      promoter. Its copy number variations are the genetic basis of isolated 46,XX and 46,XY DSDs of variable severity (ranging from mild to complete sex reversal). It is proposed that this region contains a gonad specific\n                      <jats:italic>SOX9<\/jats:italic>\n                      transcriptional enhancer(s), the gain or loss of which results in genomic imbalance sufficient to activate or inactivate\n                      <jats:italic>SOX9<\/jats:italic>\n                      gonadal expression in a tissue specific manner, switch sex determination, and result in isolated DSD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmedgenet-2011-100255","type":"journal-article","created":{"date-parts":[[2011,11,3]],"date-time":"2011-11-03T20:20:55Z","timestamp":1320351655000},"page":"825-830","source":"Crossref","is-referenced-by-count":177,"title":["Disruption of a long distance regulatory region upstream of\n                    <i>SOX9<\/i>\n                    in isolated disorders of sex 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