G708E mutation in the androgen receptor results in complete loss of androgen function.
End-organ resistance to androgens, called androgen insensitivity syndrome (AIS), is a rare disorder. The most common cause of AIS is mutations(s) in the androgen receptor (AR) gene; however, a significant number of these mutations have not been functionally analyzed. In the present study, we analyzed a case of complete AIS for mutations in the AR gene. Sequencing of the entire coding region of the AR gene revealed a 2650G>A mutation (mRNA sequence reference) in exon 4 of the gene, resulting in replacement of glycine with glutamate at codon 708 in the ligand-binding domain of the AR protein. The mutation was absent in 200 normal male individuals analyzed to look at its occurrence in general population. In vitro androgen-binding and transactivation assays showed that the mutation resulted in approximately 65% loss of ligand binding and almost complete loss of transactivation function. Complete AIS in this individual was due to a G708E substitution in the AR protein.
Rajender
Singh
S
Endocrinology Division, Central Drug Research Institute (Council of Scientific and Industrial Research), Hyderabad, India.
Pooja
Singh
S
Gupta
Nalini J
NJ
Chakrabarty
Baidyanath
B
Singh
Lalji
L
Thangaraj
Kumarasamy
K
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011944:Receptors, Androgen / Q000235:genetics*; D016415:Sequence Alignment
C410798:AR protein, human; D011944:Receptors, Androgen