{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:38:42Z","timestamp":1790883522875,"version":"4.1.0"},"reference-count":38,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report on clinical and molecular findings in five karyotypic males (cases 1\u20135) and one karyotypic female (case 6) with distal 9p monosomy. Cases 1\u20133 and 6 had female external genitalia, case 4 showed ambiguous external genitalia, and case 5 exhibited male external genitalia with left cryptorchidism and right intrascrotal testis. Gonadal explorations at gonadectomy in cases 3 and 4 revealed that case 3 had left streak gonad and right agonadism, and case 4 had bilateral hypoplastic testes. Endocrine studies in cases 1\u20134 and 6 showed that cases 1, 3, and 6 had definite primary hypogonadism, with basal FSH levels of 54, 39, and 41 IU\/L, respectively, whereas case 2 with severe malnutrition was unremarkable for the baseline values, and case 4 had fairly good testicular function. Fluorescence in situ hybridization and microsatellite analyses demonstrated that all cases had hemizygosity of the 9p sex-determining region distal to D9S1779, with loss of the candidate sex-determining genes DMRT1 and DMRT2 from the abnormal chromosome 9. Sequence analysis in cases 1\u20134 and 6 showed that they had normal sequences of each exon of DMRT1 and the DM domain of DMRT2 on the normal chromosome 9, and that cases 1\u20134 had normal SRY sequence.<\/jats:p><jats:p>The results provide further support for the presence of a sex-determining gene(s) on distal 9p and favor the possibility of DMRT1 and\/or DMRT2 being the sex-determining gene(s). Furthermore, as hemizygosity of the 9p sex-determining region was associated with a wide spectrum of gonadogenesis from agonadism to testis formation in karyotypic males and with primary hypogonadism regardless of karyotypic sex, it is inferred that haploinsufficiency of the 9p sex-determining gene(s) primarily hinders the formation of indifferent gonad, leading to various degrees of defective testis formation in karyotypic males and impaired ovary formation in karyotypic females.<\/jats:p>","DOI":"10.1210\/jcem.85.9.6771","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:06:07Z","timestamp":1389200767000},"page":"3094-3100","source":"Crossref","is-referenced-by-count":10,"title":["Sex-Determining Gene(s) on Distal 9p: Clinical and Molecular Studies in Six Cases*"],"prefix":"10.1210","volume":"85","author":[{"given":"Koji","family":"Muroya","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine (K.M., T.Ok., T.Og.), Tokyo 160-8582"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torayuki","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Department of Genetics, National Children\u2019s Medical Research Center (T.Ok.), Tokyo 154-8509"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Goishi","sequence":"additional","affiliation":[{"name":"Divisions of Neonatology (K.G.) 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