# A Very Early Diagnosis of Complete Androgen Insensitivity Syndrome Due to a Novel Variant in the AR Gene: A Neonatal Case Study

## TL;DR

A newborn with a rare genetic condition was diagnosed early due to a new mutation in the AR gene, which affects sexual development.

## Contribution

The study identifies a novel AR gene variant not previously reported in the literature or ClinVar database.

## Key findings

- A novel missense variant, c.2108C>A, in the AR gene was identified in a neonate with complete androgen insensitivity syndrome.
- The variant is predicted to have a pathogenetic effect based on computational models.
- Early diagnosis was achieved through a multidisciplinary approach including karyotype analysis and next-generation sequencing.

## Abstract

Androgen insensitivity syndrome (AIS) is one of the most common Disorders of Sexual Differentiation (DSDs). AIS is characterized by an X-linked recessive inheritance pattern associated with variants in the androgen receptor (AR) gene that affects the masculinization process in individuals with XY karyotype. Here, we report a neonatal case of a very early diagnosis of complete AIS due to a novel variant in the AR gene. In the present case, after the clinical evaluation, the infant has undergone the following tests: biochemical analyses, including newborn screening workflow, karyotype analysis, and Next-Generation Sequencing (NGS) panel of 50 genes involved in DSDs. The NGS analysis identified a missense variant, c.2108C>A, in the AR gene. According to a cytogenetic analysis, the patient presented a 46, XY karyotype, thus the resulting hemizygote for the AR gene variant. The variant is not currently described in the literature nor in the ClinVar database. However, according to computational models, the variant could have a pathogenetic effect. This clinical case reveals a novel variant of the AR gene with a possible pathogenetic effect associated with AIS and highlights the importance of a multidisciplinary approach for the timely diagnosis and appropriate follow-up of the patient.