{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:38:00Z","timestamp":1784774280146,"version":"3.55.0"},"reference-count":14,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Copy number variants that duplicate distal upstream enhancer elements of the <jats:italic>SOX9<\/jats:italic> gene cause 46,XX testicular differences of sex development (DSD) which is characterized by a 46,XX karyotype in an individual presenting with either ambiguous genitalia or genitalia with varying degrees of virilization, including those resembling typical male genitalia. Reported duplications in this region range in size from 24 to 780 kilobases (kb). Here we report a family with two affected individuals, the proband and his maternal uncle, harboring a 3.7\u2009kb duplication of a <jats:italic>SOX9<\/jats:italic> enhancer identified by clinical genome sequencing. Prior fluorescence in situ hybridization (FISH) for <jats:italic>SRY<\/jats:italic> and a multi\u2010gene panel for ambiguous genitalia were non\u2010diagnostic. The unaffected mother also carries this duplication, consistent with previously described incomplete penetrance. To our knowledge, this is the smallest duplication identified to\u2010date, most of which resides in a 5.2\u2009kb region that has been previously shown to possess enhancer activity that promotes the expression of <jats:italic>SOX9<\/jats:italic>. The duplication was confirmed by quantitative\u2010PCR and shown to be in tandem by bidirectional Sanger sequencing breakpoint analysis. This finding highlights the importance of non\u2010coding variant interrogation in suspected genetic disorders.<\/jats:p>","DOI":"10.1002\/ajmg.a.63367","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T11:22:06Z","timestamp":1691493726000},"page":"2831-2836","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The smallest likely pathogenic duplication of a <scp><i>SOX9<\/i><\/scp> enhancer identified to date in a family with 46,<scp>XX<\/scp> testicular differences of sex development"],"prefix":"10.1002","volume":"191","author":[{"given":"Samin A.","family":"Sajan","sequence":"first","affiliation":[{"name":"lllumina Clinical Services Laboratory Illumina Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn M.","family":"Brown","sequence":"additional","affiliation":[{"name":"lllumina Clinical Services Laboratory Illumina Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Davis\u2010Keppen","sequence":"additional","affiliation":[{"name":"USD Sanford School of Medicine Sanford Children's Hospital  Sioux Falls South Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Burns","sequence":"additional","affiliation":[{"name":"USD Sanford School of Medicine Sanford Children's Hospital  Sioux Falls South Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Royer","sequence":"additional","affiliation":[{"name":"USD Sanford School of Medicine Sanford Children's Hospital  Sioux Falls South Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A. 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