| Autor: |
Kikumi, Ushijima, Yuya, Ogawa, Miho, Terao, Yumi, Asakura, Koji, Muroya, Mie, Hayashi, Tomohiro, Ishii, Tomonobu, Hasegawa, Ryohei, Sekido, Maki, Fukami, Shuji, Takada, Satoshi, Narumi |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
American journal of medical genetics. Part AREFERENCES. 185(4) |
| ISSN: |
1552-4833 |
| Popis: |
SOX9, a transcription factor, is expressed in the undifferentiated XX and XY gonads. SRY induces significant upregulation of SOX9 expression in XY gonads. Loss-of-function SOX9 variants cause testicular dysgenesis in 46,XY patients, while duplication of the total gene or the upstream regulatory region results in testicular development in 46,XX patients. However, gain-of-function (GoF) SOX9 variants have not been reported previously. We report the case of a 16-year-old female patient with a 46,XX karyotype who had masculinized external genitalia and unilateral ovotestis. Next-generation sequencing-based genetic screening for disorders of sex development led to the identification of a novel SOX9 variant (p.Glu50Lys), transmitted from the phenotypically normal father. Expression analysis showed that E50K-SOX9 enhanced transactivation of the luciferase reporter containing the testis enhancer sequence core element compared with that containing the wildtype-SOX9. This GoF activity was not observed in the luciferase reporter containing Amh, the gene for anti-Müllerian hormone. We genetically engineered female mice (Sox9 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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