# Case Report: De novo DHX37 mutations in Saudi patients with 46,XY differences of sex development

## TL;DR

This paper reports on three Saudi patients with 46,XY differences of sex development caused by mutations in the DHX37 gene, highlighting the gene's role in testicular development.

## Contribution

The study presents the first case series of DHX37-related DSD in Saudi Arabia and identifies a novel mutation.

## Key findings

- Three Saudi patients with 46,XY DSD were found to have DHX37 mutations, including one novel variant.
- Phenotypic variability was observed, ranging from complete testicular regression to partial gonadal dysgenesis.
- Genetic testing, especially whole-exome sequencing, is emphasized for accurate diagnosis in high-consanguinity regions.

## Abstract

Differences of sex development (DSD) are a group of congenital conditions involving atypical chromosomal, gonadal, or anatomical sex development. DHX37, a gene involved in ribosome biogenesis, located on chromosome 12, at the 12q24.31 region, has recently emerged as a contributor to 46,XY DSD, particularly gonadal dysgenesis and testicular regression syndrome (TRS). This study presents a case series from Saudi Arabia highlighting novel and known DHX37 variants in three patients with 46,XY DSD. Three Saudi patients presented with ambiguous genitalia, non-palpable or atrophic testes, and hypergonadotropic hypogonadism. Identified variants included two known (p.Arg308Gln, p.Arg674Trp) and one novel (p.Gly478Val) missense mutation. Phenotypic variability ranged from complete testicular regression to partial gonadal dysgenesis. Thus, this is the first case series of DHX37-related DSD in Saudi Arabia, expanding the mutational spectrum and reinforcing the gene’s role in testicular development. Genetic testing, particularly whole-exome sequencing, is essential for accurate diagnosis and management, especially in regions with high consanguinity.