• PMID: 20671138
• Gene Name: AR
• Condition: AIS
• Association: Complete AIS in this individual was due to a G708E substitution in the AR protein.
• Mutation: 2650G>A (G708E)
• Population size: 1
• Population details: 1 AIS
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: AIS

G708E mutation in the androgen receptor results in complete loss of androgen function

Rajender S, Pooja S, Gupta NJ, Chakrabarty B, Singh L, Thangaraj K.

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. FAU - Rajender, Singh AU - Rajender S AD - Endocrinology Division, Central Drug Research Institute (Council of Scientific and Industrial Research), Hyderabad, India. FAU - Pooja, Singh AU - Pooja S FAU - Gupta, Nalini J AU - Gupta NJ FAU - Chakrabarty, Baidyanath AU - Chakrabarty B FAU - Singh, Lalji AU - Singh L