# Case Report: Whole-exome sequencing revealed a de novo variant in SETBP1 gene in a Chinese family with developmental delay

## TL;DR

A de novo SETBP1 gene variant was found in a child with developmental delay, highlighting the role of genetic testing in diagnosis and counseling.

## Contribution

Identification of a novel pathogenic SETBP1 variant in a Chinese family with developmental delay.

## Key findings

- A de novo nonsense variant in SETBP1 (c.1630C>T, p.Arg544Ter) was identified in a child with developmental delay.
- The variant was classified as pathogenic using ACMG guidelines and linked to intellectual disability, autosomal dominant 29 (MRD29).
- The findings emphasize the importance of early genetic testing for accurate diagnosis and reproductive guidance in developmental delay cases.

## Abstract

This study aims to characterize the potential genetic etiologies in children with developmental delay through whole-exome sequencing (WES) providing assistance for clinical diagnosis, genetic counseling, and reproductive guidance.

WES was performed on the proband, followed by Sanger sequencing validation of the identified variant in the parents.

The proband exhibits global developmental delay, including impaired motor and language development, reduced spontaneous speech, poor coordination, and attention deficits. WES revealed a heterozygous nonsense variant in SETBP1 (c.1630C>T, p.Arg544Ter), which was confirmed as de novo by Sanger sequencing. This variant was classified as pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines. The patient was subsequently diagnosed with intellectual disability, autosomal dominant 29 (MRD29).

The de novo SETBP1 p.Arg544Ter variant was identified as the underlying genetic cause in this case. Our findings underscore the importance of early genetic testing in children with developmental delay to enable precise diagnosis, informed genetic counseling, and evidence-based reproductive planning.