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

Abstract

Introduction: 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.

Material and methods: 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.

Results: 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).

Conclusions: 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.

(Endokrynol Pol 2013; 64 (5): 398–402)