# Effect of the OPHN1 novel variant c.1025+1 G>A on RNA splicing: insights from a minigene assay

## TL;DR

A new genetic variant in the OPHN1 gene is linked to developmental delay and seizures in a child, confirmed through genetic testing and RNA splicing experiments.

## Contribution

A novel OPHN1 variant is identified and shown to disrupt RNA splicing, contributing to X-linked intellectual disability.

## Key findings

- A hemizygous OPHN1 variant c.1025+1G>A was found in a child with developmental delay and seizures.
- The variant causes 56 bp intron retention, confirming its pathogenicity in X-linked intellectual disability.
- The variant was classified as likely pathogenic according to ACMG guidelines.

## Abstract

This research analyzes the clinical data, whole-exome sequencing results, and in vitro minigene functional experiments of a child with developmental delay and intellectual disability. The male patient, aged 4, began experiencing epileptic seizures at 3 months post-birth and has shown developmental delay. Rehabilitation training was administered between the ages of one and two. There were no other significant family medical histories. Through comprehensive family exome genetic testing, a hemizygous variant in the 11th exon of the OPHN1 gene was identified in the affected child: c.1025 + 1G > A. Family segregation analysis confirmed the presence of this variant in the patient’s mother, which had not been previously reported. According to the ACMG guidelines, this variant was classified as a likely pathogenic variant. In response to this variant, an in vitro minigene functional experiment was designed and conducted, confirming that the mutation affects the normal splicing of the gene’s mRNA, resulting in a 56 bp retention on the left side of Intron 11. It was confirmed that OPHN1: c.1025 + 1G > A is the pathogenic cause of X-linked intellectual disabilities in the child, with clinical phenotypes including developmental delay and seizures.

The online version contains supplementary material available at 10.1186/s12920-024-01952-1.