New NR5A1 mutations and phenotypic variations of gonadal dysgenesis
Abstract: Mutations in NR5A1 have been reported as a frequent cause of 46,XY disorders of sex development (DSD) associated to a broad phenotypic spectrum ranging from infertility, ambiguous genitalia, anorchia to gonadal dygenesis and female genitalia. Here we present the clinical follow up of four 46,XY DSD patients with three novel heterozygous mutations in the NR5A1 gene leading to a p.T40P missense mutation and a p.18DKVSG22del nonframeshift deletion in the DNA-binding domain and a familiar p.Y211Tfs*83 frameshift mutation. Functional analysis of the missense and nonframeshift mutation revealed a deleterious character with loss of DNA-binding and transactivation capacity. Both, the mutations in the DNA-binding domain, as well as the familiar frameshift mutation are associated with highly variable endocrine values and phenotypic appearance. Phenotypes vary from males with spontaneous puberty, substantial testosterone production and possible fertility to females with and without Müllerian structures and primary amenorrhea. Exome sequencing of the sibling’s family revealed TBX2 as a possible modifier of gonadal development in patients with NR5A1 mutations
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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PLOS ONE. - 12, 5 (2017) , e0176720, ISSN: 1932-6203
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2019
- Urheber
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Werner, Ralf
Mönig, Isabel
Lünstedt, Ralf
Wünsch, Lutz
Thorns, Christoph
Reiz, Benedikt
Krause, Alexandra
Schwab, Karl Otfried
Binder, Gerhard
Holterhus, Paul-Martin
Hiort, Olaf
- Beteiligte Personen und Organisationen
- DOI
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10.1371/journal.pone.0176720
- URN
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urn:nbn:de:bsz:25-freidok-1422746
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:41 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Werner, Ralf
- Mönig, Isabel
- Lünstedt, Ralf
- Wünsch, Lutz
- Thorns, Christoph
- Reiz, Benedikt
- Krause, Alexandra
- Schwab, Karl Otfried
- Binder, Gerhard
- Holterhus, Paul-Martin
- Hiort, Olaf
- Klinik für Allgemeine Kinder- und Jugendmedizin
- Universität
Entstanden
- 2019
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