# Familial novel androgen receptor gene variant associated with bilateral cryptorchidism and severe male infertility: A case report

## TL;DR

A new androgen receptor gene variant is linked to cryptorchidism and infertility in two brothers, highlighting the importance of genetic testing.

## Contribution

A novel AR gene variant (p.Tyr364His) is identified in two brothers with cryptorchidism and infertility, expanding the known mutational spectrum.

## Key findings

- A novel AR missense variant (p.Tyr364His) was found in two brothers with cryptorchidism and infertility.
- The variant is located in the N-terminal domain and is predicted to cause partial receptor dysfunction.
- This case expands the AR mutational spectrum and underscores the need for early genetic evaluation in cryptorchidism.

## Abstract

Cryptorchidism is a common congenital anomaly linked to infertility and testicular cancer risk. Variants in the androgen receptor (AR) gene cause androgen insensitivity syndrome (AIS), ranging from complete (CAIS) to partial (PAIS) and mild (MAIS) forms. We report a male patient with infertility, severe oligoasthenoteratozoospermia, and bilateral cryptorchidism. Whole-genome sequencing revealed a novel AR missense variant (p.Tyr364His) in the N-terminal domain, predicted to cause partial receptor dysfunction. The same variant was found in his brother with cryptorchidism and PAIS features. This finding expands the AR mutational spectrum and emphasizes the need for early genetic evaluation and counseling in cryptorchidism.