# Application of rapid clinical exome sequencing technology in the diagnosis of critically ill pediatric patients with suspected genetic diseases

## TL;DR

This study shows that rapid clinical exome and mitochondrial DNA sequencing can quickly diagnose genetic disorders in critically ill infants and children.

## Contribution

The study demonstrates the effectiveness of rapid clinical exome and mtDNA sequencing as primary diagnostic tools for critically ill pediatric patients.

## Key findings

- Genetic disorders were diagnosed in 56.8% of 44 critically ill pediatric patients.
- Rapid sequencing had a median turnaround time of 9.5 days and identified de novo variants in 36% of diagnosed cases.
- CES and mtDNA sequencing provided precise results that guided treatment and reduced mortality.

## Abstract

This study evaluates the efficacy of rapid clinical exome sequencing (CES) and mitochondrial DNA (mtDNA) sequencing for diagnosing genetic disorders in critically ill pediatric patients.

A multi-centre investigation was conducted, enrolling critically ill pediatric patients suspected of having genetic disorders from March 2019 to December 2020. Peripheral blood samples from patients and their parents were analyzed using CES (proband-parent) and mtDNA sequencing (proband-mother) based on Next-Generation Sequencing (NGS) technology.

The study included 44 pediatric patients (24 males, 20 females) with a median age of 27 days. The median turnaround time for genetic tests was 9.5 days. Genetic disorders were diagnosed in 25 patients (56.8%): 5 with chromosome microduplication/deletion syndromes (11.3%), 1 with UPD-related disease (2.3%), and 19 with monogenic diseases (43.2%). De novo variants were identified in nine patients (36.0%). A neonate was diagnosed with two genetic disorders due to a homozygous SLC25A20 variant and an MT-TL1 gene variation.

Rapid genetic diagnosis is crucial for critically ill pediatric patients with suspected genetic disorders. CES and mtDNA sequencing offer precise and timely results, guiding treatment and reducing mortality and disability, making them suitable primary diagnostic tools.