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Title: Investigation of androgen receptor gene DNA sequence in patients with complete or partial androgen insensitivity syndrome or unexplained infertility
Author: Tincello, Douglas G.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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Androgen insensitivity is an X-linked hereditary disorder characterised by failure of virilisation during in utero and pubertal development. The genetic basis of the disorder is now well defined with the finding that deletions or point mutations of the androgen receptor (AR) gene are present in many affected patients. The AR is an intracellular steroid receptor and acts by binding to DNA to cause transactivation of target genes. The receptor protein possesses different structural domains which are essential to effect hormone binding, DNA binding and transactivating functions. The identification of mutations within the AR gene of affected individuals has allowed the elucidation of certain key amino acids essential for receptor function. The mutations which have been identified are located throughout the gene and cause a spectrum of functional impairment from abolition of binding to subtle effects on conformational stability of the receptor/ligand complex. In the light of this it has been suggested that androgen receptor gene mutations may be responsible for infertility in otherwise normal men. DNA was extracted from whole blood obtained from six patients with complete androgen insensitivity and from nine patients with features of partial androgen insensitivity and the individual exons of the AR gene were amplified by polymerase chain reaction. Direct sequencing of the exons was performed to detect the presence of point mutations. Of the fifteen patients, point mutations were detected in three with complete androgen insensitivity and in four with partial insensitivity. Another of the patients showed an amplification of the glutamine homopolymeric repeat region of the receptor; this abnormality is known to be associated with spinal and bulbar muscular atrophy (Kennedy's disease) and a review of the case history suggested that he had an atypical presentation of this disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available