Clinical Application of Whole Exome Sequencing for Monogenic Disorders in PICU of China
Yingchao Liu1,2, Chanjuan Hao3, Kechun Li1,2
1Pediatric Intensive Care Unit, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Insights
Whole exome sequencing (WES) effectively diagnosed genetic disorders in Chinese pediatric intensive care units (PICUs). This genetic testing significantly impacted patient treatment and care management.
Area of Science:
- Genomics
- Pediatric Critical Care Medicine
- Medical Genetics
Background:
- Whole exome sequencing (WES) is a powerful tool for diagnosing genetic disorders.
- Data on WES utility in Chinese pediatric intensive care units (PICUs) is limited.
- Monogenic disorders present diagnostic challenges in critically ill children.
Purpose of the Study:
- To investigate the spectrum of monogenic disorders in a Chinese PICU.
- To determine the diagnostic yield of WES in critically ill children.
- To assess the clinical utility and impact of WES on patient management.
Main Methods:
- Whole exome sequencing (WES) was performed on 169 critically ill children with suspected monogenic diseases.
- Clinical features and Human Phenotype Ontology (HPO) terms were analyzed.
- The impact of WES results on treatment decisions was evaluated.
Main Results:
- A diagnosis of monogenic disorder was achieved in 25% of patients (43/169).
- Metabolic diseases, neuromuscular disorders, and multiple deformities were the most common diagnoses.
- WES results influenced treatment in 70% of diagnosed cases, including treatment changes and care redirection.
Conclusions:
- Whole exome sequencing (WES) is an effective diagnostic method for critically ill children in Chinese PICUs.
- WES provides valuable clinical utility, significantly impacting patient treatment and management.
- This study highlights the importance of genetic testing in diagnosing rare diseases in pediatric critical care settings.
Objectives:
Whole exome sequencing (WES) has been widely used to detect genetic disorders in critically ill children. Relevant data are lacking in pediatric intensive care units (PICUs) of China. This study aimed to investigate the spectrum of monogenic disorders, the diagnostic yield and clinical utility of WES from a PICU in a large children's hospital of China.
Methods:
From July 2017 to February 2020, WES was performed in 169 critically ill children with suspected monogenic diseases in the PICU of Beijing Children's Hospital. The clinical features, human phenotype ontology (HPO) terms, and assessment of clinical impact were analyzed.
Results:
The media age of the enrolled children was 10.5 months (range, 1 month to 14.8 years). After WES, a total of 43 patients (25%) were diagnosed with monogenic disorders. The most common categories of diseases were metabolic disease (33%), neuromuscular disease (19%), and multiple deformities (14%). The diagnosis yield of children with "metabolism/homeostasis disorder" and "growth delay" or "ocular anomalies" was higher than that of children without these features. In addition, the diagnosis rate increased when more features were observed in children. The results of WES had an impact on the treatment for 30 cases (70%): (1) change of treatment (n = 11), (2) disease monitoring initiation (n = 18), (3) other systemic evaluation (n = 3), (4) family intervention (n = 2), and (5) rehabilitation and redirection of care toward palliative care (n = 12).
Conclusion:
WES can be used as an effective diagnostic tool in the PICU of China and has an important impact on the treatment of patients with suspected monogenic conditions.
