Mutational analysis of androgen receptor gene in two families with androgen insensitivity

Abstract

Background:Androgen insensitivity syndrome (AIS) is a rare X-linked disorder due to mutations in the androgen receptor (AR) gene causing end-organ resistance to the androgenic hormone.Subjects and Methods:Genetic studies were carried out in two families by karyotype and targeted exome sequencing of the AR gene.Results:Two novel missense mutations were identified, p.L822P and p.P392S, in two families with complete androgen insensitivity (CAIS) and partial androgen insensitivity (PAIS), respectively. Both had 46, XY karyotype. The mother was a heterozygous carrier in PAIS and negative in CAIS. These two were novel mutations, reported for the first time, in the AR gene. In silico analysis predicted that both mutations were damaging. We reviewed the various reported Indian mutations in the AR gene.Conclusion:AR gene mutations cause a wide spectrum of disorders from CAIS to male infertility or primary amenorrhea. Early diagnosis is essential for gender assignment and further management, family counseling, and prenatal diagnosis.

Clinical, Biochemical, and Molecular Characterization of Indian Children with Clinically Suspected Androgen Insensitivity Syndrome

“…More than 1,100 different pathogenic variants including deletions, duplications, insertions, and point variants have been documented in the AR gene (www.androgendb.mcgill.ca), with the majority being missense pathogenic variants. There are very few studies from India on clinical, biochemical, and molecular aspects of AIS, the majority being case reports [Abilash et al, 2016;Saranya et al, 2016;Akella, 2017], and no hotspot pathogenic variant has been identified [Nagaraja et al, 2010].…”