دورية أكاديمية
The novel mutation p.Trp147Arg of the steroidogenic acute regulatory protein causes classic lipoid congenital adrenal hyperplasia with adrenal insufficiency and 46,XY disorder of sex development
| العنوان: | The novel mutation p.Trp147Arg of the steroidogenic acute regulatory protein causes classic lipoid congenital adrenal hyperplasia with adrenal insufficiency and 46,XY disorder of sex development |
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| المؤلفون: | Yüksel B., Kulle A.E., Gürbüz F., Welzel M., Kotan D., Mengen E., Holterhus P.-M. |
| المساهمون: | Çukurova Üniversitesi |
| بيانات النشر: | S. Karger AG |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adrenal insufficiency, Disorder of sex development, Lipoid congenital adrenal hyperplasia, Sex reversal, Steroid synthesis |
| الوصف: | PubMedID: 23920000 ; Background: The steroidogenic acute regulatory protein (StAR) is essential for steroidogenesis by mediating cholesterol transfer into mitochondria. Inactivating StAR mutations cause lipoid congenital adrenal hyperplasia. Objective and Methods: To identify causative mutations in a patient presenting with adrenal failure during early infancy. The objective was to study the functional and structural consequences of the novel StAR mutation p.Trp147Arg in a Turkish patient detected in compound heterozygosity with the p.Glu169Lys mutation. Results: Transient in vitro expression of the mutant proteins together with P450 side-chain cleavage enzyme, adrenodoxin, and adrenodoxin reductase yielded severely diminished cholesterol conversion of the p.Trp147Arg mutant. The previously described p.Glu169Lys mutant led to significantly lower cholesterol conversion than wild-type StAR protein. As derived from three-dimensional protein modeling, the residue W147 is stabilizing the C-terminal helix in a closed conformation hereby acting as gatekeeper of the ligand cavity of StAR. Conclusions: The novel mutation p.Trp147Arg causes primary adrenal insufficiency and complete sex reversal in the 46,XY patient. Clinical disease, in vitro studies and three-dimensional protein modeling of the mutation p.Trp147Arg underscore the relevance of this highly conserved residue for StAR protein function. Copyright © 2013 S. Karger AG, Basel. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1663-2818 |
| العلاقة: | Hormone Research in Paediatrics; Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı; https://dx.doi.org/10.1159/000354086Test; https://hdl.handle.net/20.500.12605/21651Test; 80; 163; 169 |
| DOI: | 10.1159/000354086 |
| الإتاحة: | https://doi.org/20.500.12605/21651Test https://doi.org/10.1159/000354086Test https://hdl.handle.net/20.500.12605/21651Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.D3660665 |
| قاعدة البيانات: | BASE |
| تدمد: | 16632818 |
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| DOI: | 10.1159/000354086 |