| Autor: |
Annik Hauri-Hohl, Monika Meyer-Böni, Mariarosaria Lang-Muritano, Anna Biason-Lauber, Eugen J. Schoenle, Mathias Hauri-Hohl |
| Rok vydání: |
2011 |
| Předmět: |
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| Zdroj: |
Clinical Endocrinology. 75:39-43 |
| ISSN: |
0300-0664 |
| Popis: |
Context Aromatase deficiency in females is a rare 46,XX Disorder of Sex Differentiation characterized by a defect in catalyzing ooestrogens from androgens. Objective To better understand this rare disorder, we searched for mutations in the CYP19A1 gene of an affected girl and analyzed their functional consequences. Design and Patient We examined a girl presenting with clitoral hypertrophy at birth and mild maternal virilization (acne) during pregnancy. Main Outcome Measurement A genotype-phenotype correlation was found. Results By direct sequencing of the CYP19A1 gene we identified a heterozygous A>G mutation (c. A1374G) mutation in exon IX, leading to the missense p.N411S in the P450Aro protein and a heterozygous placenta promoter variant -41 base pairs upstream of exon I.1. Aromatase enzyme activity was completely lost when the mutant p.N411S protein was expressed in COS1 cells. The placenta promoter variant had a significantly reduced (-50%) transactivation ability compared to wild type. Conclusion Our data describe a novel loss-of-function missense mutation in CYP19A1 combined with the first described variant of the placenta promoter with a significant reduction in function, likely to be the molecular basis of this rare 46, XX disorder of sex development. This seems to represent a unique case of aromatase deficiency occuring in utero only. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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