A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism
| Autor: | Veronique Bex, Xavier Bertagna, Philippe Bouchard, Dominique Recan, John C. Achermann, Antoine Tabarin, Masafumi Ito, Sophie Christin-Maitre, J. Larry Jameson |
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| Předmět: |
Adult
Male medicine.medical_specialty Receptors Retinoic Acid Biology Article Primary Adrenal Insufficiency Mice Hypogonadotropic hypogonadism Internal medicine X-linked adrenal hypoplasia congenita Adrenal Glands medicine Adrenal insufficiency Animals Humans Missense mutation Age of Onset Mice Knockout DAX-1 Orphan Nuclear Receptor Hypogonadism Adrenal hypoplasia General Medicine medicine.disease DNA-Binding Proteins Repressor Proteins Endocrinology Congenital adrenal hypoplasia Mutation DAX1 Transcription Factors |
| Zdroj: | Scopus-Elsevier |
| Popis: | Mutations in the DAX1 gene cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). In affected boys, primary adrenal insufficiency occurs soon after birth or during early childhood; HHG is recognized at the expected time of puberty. In this report, we describe the novel phenotype of a man who presented with apparently isolated adrenal insufficiency at 28 years of age. Examination revealed partial pubertal development and undiagnosed incomplete HHG. Gonadotropin therapy did not improve his marked oligospermia, suggesting a concomitant primary testicular abnormality. Genomic analysis revealed a novel missense mutation, I439S, in DAX1. The mutant DAX-1 protein was studied for its ability to function as a transcriptional repressor of target genes. Consistent with the patient’s mild clinical phenotype, the I439S mutation conferred intermediate levels of repressor activity of DAX-1 when compared with mutations associated with classic AHC. This unique case extends the clinical spectrum of AHC to include delayed-onset primary adrenal insufficiency in adulthood and milder forms of HHG. Furthermore, in accordance with findings in Ahch (Dax1) knockout mice, the clinical features in this patient suggest that DAX-1 function is required for spermatogenesis in humans, independent of its known effects on gonadotropin production. |
| Databáze: | OpenAIRE |
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