Mutational analysis of the androgen receptor gene in two Chinese families with complete androgen insensitivity syndrome.
Androgens are essential for normal male sex differentiation and are responsible for the normal development of male secondary sexual characteristics at puberty. The physiological effects of androgens are mediated by the androgen receptor (AR). Mutations in the AR gene are the most common cause of androgen insensitivity syndrome. The present study undertook a genetic analysis of the AR gene in two unrelated families affected by complete androgen insensitivity syndrome (CAIS) in China. In family 1, a previously reported nonsense mutation (G-to-A; p.W751X) was identified in exon 5 of theARgene. In addition, a novel missense mutation was detected in exon 6 of theARgene from family 2; this mutation resulted in a predicted amino acid change from phenylalanine to serine at codon 804 (T-to-C; p.F804S) in the ligand-binding domain (LBD) of AR. Computer simulation of the structural changes generated by the p.F804S substitution revealed marked conformational alterations in the hydrophobic core responsible for the stability and function of the AR-LBD. In conclusion, the present study identified two mutations from two unrelated Chinese families affected by CAIS. The novel mutation (p.F804S) may provide insights into the molecular mechanism underlying CAIS. Furthermore, it expands on the number of mutational hot spots in the international AR mutation database, which may be useful in the future for prenatal diagnosis and genetic counseling.
Department of Urology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Song
S
Wang
Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Haikun
H
Xu
Department of Urology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Wei
W
An
Department of Urology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Dechun
D
Zhu
Center for Prenatal Diagnosis, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Dejun
D
Li
androgen receptor; complete androgen insensitivity syndrome; novel mutation; structural analysis