Abstract
Germinal point mutations within the androgen receptor (AR) gene cause a heterogenous group of androgen insensitivity syndromes (AIS). Assessment of residual function of AR mutants is important for gender assignment and prediction of pubertal development in patients with AIS. We have used an in vivo test involving the sex hormone-binding globulin (SHBG) decline in response to the anabolic steroid stanozoto! (1) to characterize androgen sensitivity in subjects with partial AIS in whom a distinct mutation of the AR gene has been defined (2). Patients: Subject 1 has a female phenotype with subtle narrowing of the vaginal introitus without clitoral enlargement. Subjects 2 and 3 are brothers who initially presented with micropenis and hypospadias, and at the time of puberty developed gynecomastia.
Results: A G→A transversion causing an arginine to histidine exchange in position 840 of the AR gene was characterized in patient 1. SHBG fell to 81% of initial value. In patients 2 and 3 a G→T substitution leads to a valine to leucine exchange in codon 866. Patient 2 had a SHBG decline to 66%, while his brother had a decline to 7156 of initial value.
Conclusion: Studies of patients carrying AR mutants using the SHBG test in vivo may provide physiologically relevant functional information about the AR and may permit clinically valuable genotype-phenotype prediction. Further tests in patients with AR mutations are in progress.
1. Sinnecker GHG, Köhler S: J Clin Endocrinol Metab 1989; 68, 1195
2. Hiort et al.: Am J Hum Genet 1992; 51 (4), A 170
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Hiort, O., Sinnecker, G. FUNCTIONAL ASSESSMENT OF ANDROGEN RECEPTOR MUTANTS IN VIVO. Pediatr Res 33 (Suppl 5), S17 (1993). https://doi.org/10.1203/00006450-199305001-00084
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DOI: https://doi.org/10.1203/00006450-199305001-00084