Abstract
The aim of this study is to evaluate the genetic abnormalities that led to a diagnosis of glucocorticoid resistance syndrome (GRS) in a young woman presenting with hirsutism and irregular menstrual cycles. A 16-yr-old girl presented with acne and hirsutism since menarche and recent secondary amenorrhea. The patient had borderline hypertension, but no signs of hypercortisolism. She had an intact circadian rhythm of circulating ACTH and cortisol. Higher than normal oral doses of dexamethasone were required to decrease her serum cortisol significantly. We performed single-strand conformation polymorphism (SSCP) analysis to screen the gene encoding the isoform α of glucocorticoid receptor (GRα). Amplicons displaying abnormal migration pattern were subjected to direct sequencing. We found the patient heterozygous for a novel point mutation of GRα in exon 6 (Leu595→Val), which yielded molecular structure, with functional consequences based on comparative molecular modeling of the ligand binding domain (LBD) of the wild-type and mutant GRα. She was also heterozygous for a silent mutation in exon 9 (Asn766→Asn). We demonstrated that GRS was associated with a novel point mutation in the LBD of GRα gene that apparently modifies the binding to dexamethasone, in a young woman.
Original language | English |
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Pages (from-to) | 105-112 |
Number of pages | 8 |
Journal | International Journal on Disability and Human Development |
Volume | 6 |
Issue number | 1 |
Publication status | Published - Jan 2007 |
Keywords
- Glucocorticoid
- Glucocorticoid hormone resistance
- Glucocorticoid receptor mutations
- Hirsutism
- Menstrual abnormalities
ASJC Scopus subject areas
- Rehabilitation
- Geriatrics and Gerontology
- Advanced and Specialised Nursing
- Psychiatry and Mental health
- Sensory Systems
- Speech and Hearing