caa a22 4500 397574088 CHVBK 20180308164850.0 cr unu---uuuuu 161202e199602 xx s 000 0 eng 10.1093/hmg/5.2.265 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.2.265 Functional Analysis of Six Androgen Receptor Mutations Identified in Patients with Partial Androgen Insensitivity Syndrome [Elektronische Daten] [Charlotte L. Bevan, Betty B. Brown, Helen R. Davies, Bronwen A. J. Evans, Ieuan A. Hughes, Mark N. Patterson] Partial androgen insensitivity syndrome (PAIS) is caused by defects in the androgen receptor gene and presents with a wide range of undervirilization pheno-types. We studied the consequences of six androgen receptor ligand-binding domain mutations on receptor function in transfected cells. The mutations, Met742Ile, Met780Ile, Gln798Glu, Arg840Cys, Arg855His and Ile869Met, were identified in PAIS patients with pheno-types representing the full spectrum seen in this condition. In all cases the androgen receptor was found to be defective, suggesting that the mutation is the cause of the clinical phenotype. The Gln798Glu mutation is exceptional in that it did not cause an androgen-binding defect in our system, although the mutant receptor was defective assays. This mutation may affect an aspect of binding not tested, or may be part of a functional subdomain of the ligand-binding domain involved in transactivation. Overall we found milder mutations to be associated with milder clinical phenotypes. There is also clear evidence that pheno-type is not solely dependent on androgen receptor function. Some of the mutant receptors were able to respond to high doses of androgen in vitro, suggesting that patients carrying these mutations may be the best candidates for androgen therapy. One such mutation is Ile869Met. A patient carrying this mutation has virilized spontaneously at puberty, so in vivo evidence agrees with the experimental result. Thus a more complete understanding of the functional consequences of androgen receptor mutations may provide a more rational basis for gender assignment in PAIS. © 1996 Oxford University Press Bevan Charlotte L. University Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK aut Brown Betty B. University Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK aut Davies Helen R. University Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK aut Evans Bronwen A. J. University Department of Child Health, University of Wales College of Medicine, Cardiff CF4 4XN, UK aut Hughes Ieuan A. University Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK aut Patterson Mark N. University Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK aut Human Molecular Genetics Oxford University Press 5/2(1996-02), 265-273 0964-6906 5:2<265 1996 5 hmg https://doi.org/10.1093/hmg/5.2.265 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.2.265 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bevan Charlotte L. University Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK aut NATIONALLICENCE 700 1- Brown Betty B. University Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK aut NATIONALLICENCE 700 1- Davies Helen R. University Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK aut NATIONALLICENCE 700 1- Evans Bronwen A. J. University Department of Child Health, University of Wales College of Medicine, Cardiff CF4 4XN, UK aut NATIONALLICENCE 700 1- Hughes Ieuan A. University Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK aut NATIONALLICENCE 700 1- Patterson Mark N. University Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/2(1996-02), 265-273 0964-6906 5:2<265 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford