Abstract
Introduction. AR belongs to a family of ligand-induced transcription factors, and its normal function is to control the differentiation, development and maintenance of male reproductive function. Complete (CAIS) and partial (PAIS) androgen insensitivity syndrome are X-linked disorders occuring in 46,XY patients and leading respectively to a female phenotype and an undermasculinized male. We have determined the AR binding capacity on genital skin fibroblasts and studied the AR gene in the DNA of 5 patients with CAIS and one patients with PAIS. Families. All patients with CAIS were characterized by a referred to our clinic for genital bud, cryptorchidism and perineal hypospadias. Two maternal uncles had ambiguous genitalia.
Methods. AR binding capacity was determined on genital skin fibroblasts (GSF) using [3H]-R 1881. Point mutations were detected by SSCP analysis of exons 2-7 of the AR gene on DNA from white blood cells and identified after direct DNA sequencing.
Results. AR binding capacity (Bmax). dissociation constant (Kd) and detected mutations are reported in the table below. Normal Bmax = 65 ± 200 fmol/mg DNA. Normal Kd = 0.6 ± 0.3 nM.
Discussion. In these families, we detected only amino acid substitution. In two cases (indicated by †), a new restriction site was created which made possible the carrier diagnosis of patients's sisters. Patients 3 presented a de novo mutation. In 2 cases (indicated by 0) a restriction site was abolished and carrier diagnosis was possible. In family 6, we found a mutation reported threefold indicating a hot-spot amino acid. As expected, the mutation described within the DNA-binding domain did not alter the AR binding capacity (patients 1 and 2). Further receptor studies are currently underway to support the potential androgen-AR and DNA-AR affinity changes.
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Lohaccaro, J., Lumbroso, S., Belon, C. et al. ANDROGEN RECEPTOR (AR) GENE MUTATIONS IN 6 FAMLIES WITH ANDROGEN INSENSITIVITY SYNDROME. Pediatr Res 33 (Suppl 5), S22 (1993). https://doi.org/10.1203/00006450-199305001-00115
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DOI: https://doi.org/10.1203/00006450-199305001-00115