A novel mutation (c.T3816 > C) in the androgen receptor gene in a 46,XY female patient with androgen insensitivity syndrome

Abstract

Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD), and are associated with a variety of phenotypes ranging from phenotypic women (Complete Androgen Insensitivity Syndrome or CAIS) to milder degrees of undervirilisation (Partial Androgen Insensitivity Syndrome or PAIS) or men with infertility only (Mild Androgen Insensitivity Syndrome or MAIS). In this paper, we present the results of clinical, endocrine and molecular trials in a patient hospitalised because of primary amenorrhoea with typical phenotype of CAIS. The main objective of this study was to determine the molecular cause of androgen insensitivity syndrome in a 46,XY female patient. Molecular analysis of the AR gene was conducted using MSSCP (Multitemperature Single Strand Conformation Polymorphism) and sequencing methods. MSSCP analysis showed changes in electrophoretic mobility in exon 8 of the AR gene. Sequencing analysis revealed a missense mutation which has not been previously described. This is a c.T3816 > C transition mutation which causes a S901P substitution in the amino acid chain (based on the latest NCBI reference sequence NM 000044.2). The identified c.T3816 > C mutation in AR gene provides further evidence for the correlation between specific AR mutations and phenotype corresponding to androgen insensitivity.