ANDROGEN RECEPTOR GENE-MUTATIONS IDENTIFIED BY SSCP IN 14 SUBJECTS WITH ANDROGEN INSENSITIVITY SYNDROME

被引:132
作者
BATCH, JA
WILLIAMS, DM
DAVIES, HR
BROWN, BD
EVANS, BAJ
HUGHES, IA
PATTERSON, MN
机构
[1] UNIV CAMBRIDGE, ADDENBROOKES HOSP, DEPT PAEDIAT, CAMBRIDGE CB2 2QQ, England
[2] UNIV WALES COLL MED, DEPT CHILD HLTH, CARDIFF CF4 4XN, S GLAM, Wales
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1093/hmg/1.7.497
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The androgen insensitivity syndrome (AIS) is a disorder of male sexual development resulting in a wide range of clinical phenotypes. AIS is classified into two phenotypic forms: complete (CAIS) and partial (PAIS). To determine the molecular basis of the phenotypic diversity in AIS, we have studied 27 subjects (13 CAIS, 14 PAIS), spanning the full range of AIS phenotypes. We report the results of a mutation screen of the androgen receptor gene. The coding regions of the gene were amplified by the polymerase chain reaction and screened for single strand conformation polymorphisms to identify mutations. This was followed by DNA sequencing of putative mutant segments. Androgen receptor gene mutations were identified in nine CAIS and rive PAIS subjects. Two of the CAIS mutations in exon A resulted in frameshifts. A third CAIS mutation resulted in the deletion of a single amino acid from the ligand binding domain of the receptor. All other mutations caused single amino acid substitutions in the ligand binding domain. These results suggest that mutations affecting the ligand binding domain of the androgen receptor are the most frequent cause of AIS, although some cases of PAIS may be the result of other, as yet undefined, genetic lesions.
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收藏
页码:497 / 503
页数:7
相关论文
共 44 条
[1]   THE FREQUENCY OF ANDROGEN RECEPTOR DEFICIENCY IN INFERTILE MEN [J].
AIMAN, J ;
GRIFFIN, JE .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1982, 54 (04) :725-732
[2]  
BATCH J, 1992, IN PRESS REPROD MED
[3]   GENE-REGULATION BY STEROID-HORMONES [J].
BEATO, M .
CELL, 1989, 56 (03) :335-344
[4]  
BOUCHARD P, 1986, J CLIN ENDOCR METAB, V63, P1241
[5]   FUNCTIONAL-CHARACTERIZATION OF NATURALLY-OCCURRING MUTANT ANDROGEN RECEPTORS FROM SUBJECTS WITH COMPLETE ANDROGEN INSENSITIVITY [J].
BROWN, TR ;
LUBAHN, DB ;
WILSON, EM ;
FRENCH, FS ;
MIGEON, CJ ;
CORDEN, JL .
MOLECULAR ENDOCRINOLOGY, 1990, 4 (12) :1759-1772
[7]   STEROID-RECEPTOR FAMILY - STRUCTURE AND FUNCTIONS [J].
CARSONJURICA, MA ;
SCHRADER, WT ;
OMALLEY, BW .
ENDOCRINE REVIEWS, 1990, 11 (02) :201-220
[8]   MOLECULAR-CLONING OF HUMAN AND RAT COMPLEMENTARY-DNA ENCODING ANDROGEN RECEPTORS [J].
CHANG, CS ;
KOKONTIS, J ;
LIAO, SS .
SCIENCE, 1988, 240 (4850) :324-326
[9]  
CHANG YT, 1991, 73RD ANN M END SOC W, P37
[10]   A FRAMESHIFT MUTATION DESTABILIZES ANDROGEN RECEPTOR MESSENGER-RNA IN THE TFM MOUSE [J].
CHAREST, NJ ;
ZHOU, ZX ;
LUBAHN, DB ;
OLSEN, KL ;
WILSON, EM ;
FRENCH, FS .
MOLECULAR ENDOCRINOLOGY, 1991, 5 (04) :573-581