Single nucleotide substitution of the androgen receptor gene in a case with receptor-positive androgen insensitivity syndrome (complete form).
Complete androgen insensitivity syndrome is caused by X chromosome linked disorder resulting in a target organ insensitivity to androgen. Two variants have been described in this syndrome. In the first, the binding of [3H]dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one) to the androgen receptor is undetectable (receptor-negative), whereas in the second variant normal levels of androgen receptor are detectable but the binding of [3H] dihydrotestosterone to the androgen receptor is significantly thermolabile under certain conditions (receptor-positive). In receptor-negative cases, genetic disorders of the androgen receptor gene have been demonstrated. On the other hand, the genetic disorder of androgen receptor in receptor-positive cases is little known. In this study, the gene structure of androgen receptor in a receptor-positive case using a polymerase chain reaction technique is studied in the fibroblasts cultured from genital skin. The results demonstrate that the substitution of nucleotide (guanine-->cytosine) in exon G of the androgen receptor causes the replacement of an amino acid in position 820 (glycine-->alanine) which occurs in the hormone-binding domain of the androgen receptor. The substitution of nucleotide may explain the thermolability of the androgen receptor in a case with receptor-positive androgen insensitivity syndrome.
Kasumi
H
H
Department of Obstetrics and Gynecology, Hyogo Medical College, Japan.
Komori
S
S
Yamasaki
N
N
Shima
H
H
Isojima
S
S
D000328:Adult; D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D003596:Cytosine / Q000737:chemistry; D004247:DNA / Q000302:isolation & purification; D013196:Dihydrotestosterone / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005998:Glycine / Q000737:chemistry; D006147:Guanine / Q000737:chemistry; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012729:Sex Chromosome Aberrations / Q000235:genetics*
D015345:Oligonucleotide Probes; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D006147:Guanine; D003596:Cytosine; D004247:DNA; D000409:Alanine; D005998:Glycine