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Current understanding of the phenotypic variability and mutation spectrum of <jats:italic><jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content>9<\/jats:italic> abnormalities remains fragmentary. Here, we report three patients with hitherto unreported <jats:italic><jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content>9<\/jats:italic> abnormalities. These patients were identified through molecular analysis of 33 patients with 46,<jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content> disorders of sex development (<jats:styled-content style=\"fixed-case\">DSD<\/jats:styled-content>). Patients 1\u20133 manifested testicular dysgenesis or regression without CD. Patients 1 and 2 carried probable damaging mutations p.Arg394Gly and p.Arg437Cys, respectively, in the <jats:italic><jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content>9<\/jats:italic> C\u2010terminal domain but not in other known 46,<jats:styled-content style=\"fixed-case\">XY DSD<\/jats:styled-content> causative genes. These substitutions were absent from ~120,000 alleles in the exome database. These mutations retained normal transactivating activity for the <jats:italic>Col2a1<\/jats:italic> enhancer, but showed impaired activity for the <jats:italic>Amh<\/jats:italic> promoter. Patient 3 harbored a maternally inherited ~491\u00a0kb <jats:italic><jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content>9<\/jats:italic> upstream deletion that encompassed the known 32.5\u00a0kb <jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content> sex reversal region. Breakpoints of the deletion resided within nonrepeat sequences and were accompanied by a short\u2010nucleotide insertion. The results imply that testicular dysgenesis and regression without skeletal dysplasia may be rare manifestations of <jats:italic><jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content>9<\/jats:italic> abnormalities. Furthermore, our data broaden pathogenic <jats:italic><jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content>9<\/jats:italic> abnormalities to include C\u2010terminal missense substitutions which lead to target\u2010gene\u2010specific protein dysfunction, and enhancer\u2010containing upstream microdeletions mediated by nonhomologous end\u2010joining.<\/jats:p>","DOI":"10.1002\/mgg3.165","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T16:18:44Z","timestamp":1436890724000},"page":"550-557","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Testicular dysgenesis\/regression without campomelic dysplasia in patients carrying missense mutations and upstream deletion of <i><scp>SOX<\/scp>9<\/i>"],"prefix":"10.1002","volume":"3","author":[{"given":"Yuko","family":"Katoh\u2010Fukui","sequence":"first","affiliation":[{"name":"Department of Molecular Endocrinology National 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