# Clinical phenotype and genetic analysis of patients with severe oligoasthenospermia carrying heterozygous SOHLH1 c.346-1G>A mutation

## TL;DR

This study identifies a genetic mutation in the SOHLH1 gene linked to severe male infertility and describes its clinical effects.

## Contribution

First evidence linking a heterozygous SOHLH1 c.346-1G>A mutation to severe oligoasthenospermia and its clinical phenotype.

## Key findings

- Patients with the SOHLH1 c.346-1G>A mutation showed severely reduced sperm counts and impaired motility.
- The mutation was associated with pronounced sperm morphological deformities.
- One patient achieved successful pregnancy through intracytoplasmic sperm injection.

## Abstract

Severe oligoasthenospermia (SOA) is a prevalent cause of male infertility. However, the underlying causes of most SOA cases remain unclear due to the complexity of germ cell development and the significant genetic heterogeneity associated with male infertility. Therefore, in this study, we aimed to elucidate the genetic etiology of two cases of male infertility resulting from SOA and clarify the novel clinical phenotype associated with a heterozygous mutation at the c.346-1G>A site of the SOHLH1 gene.

Through whole-exome sequencing, we found that patients with SOA carried heterozygous mutations at the c.346-1G>A site. This variant is classified as pathogenic based on disease database records and literature reports. Notably, our study demonstrated that patients with heterozygous mutations at the c.346-1G>A site exhibited severely reduced sperm counts, significantly impaired sperm motility, and pronounced morphological deformities. One patient underwent assisted reproductive treatment through an intracytoplasmic sperm injection and achieved a favorable outcome, resulting in a successful pregnancy.

In conclusion, our study provides the first evidence that the heterozygous mutation at the c.346-1G>A site of SOHLH1 is associated with SOA, and elucidates the new clinical phenotype associated with this mutation.