{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:28:45Z","timestamp":1782790125582,"version":"3.54.5"},"reference-count":26,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,12]],"date-time":"2023-11-12T00:00:00Z","timestamp":1699747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Disorders of sexual development (DSDs) encompass a group of congenital conditions associated with atypical development of internal and external genital structures. Among those with DSDs are 46,XX males, whose condition mainly arises due to the translocation of SRY onto an X chromosome or an autosome. In the few SRY-negative 46,XX males, overexpression of other pro-testis genes or failure of pro-ovarian\/anti-testis genes may be involved, even if a non-negligible number of cases remain unexplained. A three-year-old boy with an SRY-negative 46,XX karyotype showed a normal male phenotype and normal prepubertal values for testicular hormones. A heterozygous de novo in tandem duplication of 50,221 bp, which encompassed exons 2 and 3 of the Doublesex and Mab-3-related transcription factor 1 (DMRT1) gene, was detected using MPLA, CGH-array analysis, and Sanger sequencing. Both breakpoints were in the intronic regions, and this duplication did not stop or shift the coding frame. Additional pathogenic or uncertain variants were not found in a known pro-testis\/anti-ovary gene cascade using a custom NGS panel and whole genome sequencing. The duplication may have allowed DMRT1 to escape the transcriptional repression that normally occurs in 46,XX fetal gonads and thus permitted the testicular determination cascade to switch on. So far, no case of SRY-negative 46,XX DSD with alterations in DMRT1 has been described.<\/jats:p>","DOI":"10.3390\/genes14112067","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T02:10:43Z","timestamp":1699841443000},"page":"2067","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development"],"prefix":"10.3390","volume":"14","author":[{"given":"Veronica","family":"Bertini","sequence":"first","affiliation":[{"name":"Section of Cytogenetics, Department of Laboratory Medicine, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvia","family":"Baldinotti","sequence":"additional","affiliation":[{"name":"Section of Molecular Genetics, Department of Laboratory Medicine, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Parma","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Environmental Sciences, University of Milan, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Tyutyusheva","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Department of Obstretics, Gynecology and Pediatrics, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Sepich","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Department of Obstretics, Gynecology and Pediatrics, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Bertolucci","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Department of Obstretics, Gynecology and Pediatrics, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2949-9215","authenticated-orcid":false,"given":"Camillo","family":"Rosano","sequence":"additional","affiliation":[{"name":"Proteomics and Mass Spectrometry Unit, Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0589-1829","authenticated-orcid":false,"given":"Maria Adelaide","family":"Caligo","sequence":"additional","affiliation":[{"name":"Section of Molecular Genetics, Department of Laboratory Medicine, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Peroni","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Department of Obstretics, Gynecology and Pediatrics, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Valetto","sequence":"additional","affiliation":[{"name":"Section of Cytogenetics, Department of Laboratory Medicine, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1264-3284","authenticated-orcid":false,"given":"Silvano","family":"Bertelloni","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Department of Obstretics, Gynecology and Pediatrics, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/978-3-319-31973-5_13","article-title":"The battle of the sexes: Human sex development and its disorders","volume":"58","year":"2016","journal-title":"Results Probl. 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