L712V mutation in the androgen receptor gene causes complete androgen insensitivity syndrome due to severe loss of androgen function.

Steroids 2013 Dec 19;78(12-13):1288-92. Epub 2013 Sep 19.

Endocrinology Division, Central Drug Research Institute (Council of Scientific and Industrial Research), India. Electronic address:

Inability to respond to the circulating androgens is named as androgen insensitivity syndrome (AIS). Mutations in the androgen receptor (AR) gene are the most common cause of AIS. A cause and effect relationship between some of these mutations and the AIS phenotype has been proven by in vitro studies. Several other mutations have been identified, but need to be functionally validated for pathogenicity. Screening of the AR mutations upon presumptive diagnosis of AIS is recommended. We analyzed a case of complete androgen insensitivity syndrome (CAIS) for mutations in the AR gene. Sequencing of the entire coding region revealed C>G mutation (CTT-GTT) at codon 712 (position according to the NCBI database) in exon 4 of the gene, resulting in replacement of leucine with valine in the ligand-binding domain of the AR protein. No incidence of this mutation was observed in 230 normal male individuals analyzed for comparison. In vitro androgen binding and transactivation assays using mutant clone showed approximately 71% loss of ligand binding and about 76% loss of transactivation function. We conclude that CAIS in this individual was due to L712V substitution in the androgen receptor protein.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.steroids.2013.09.004DOI Listing
December 2013
29 Reads

Publication Analysis

Top Keywords

insensitivity syndrome
12
androgen insensitivity
12
androgen receptor
12
complete androgen
8
androgen
8
receptor gene
8
mutations
5
sequencing entire
4
mutations gene
4
mutant clone
4
gene sequencing
4
cais mutations
4
coding region
4
revealed c>g
4
c>g mutation
4
region revealed
4
assays mutant
4
syndrome cais
4
entire coding
4
recommended analyzed
4

Similar Publications