Whole exome sequencing as the first-tier test for patients in neonatal intensive care unit: A Chinese single-center study

Abstract

Abstract Background: Genetic disorders are the part of critical patients in neonatal intensive care unit, it is difficult to establish the diagnosis of pathogenesis via rountine detections and accessory examination. Whole exome sequencing may provide the evidence based on molecular diagnose for genetic disorders. Our aim was to explore the significance of whole exome sequencing for patients in neonatal intensive care unit by the retrospective observational study in a Chinese cohort of neonates. Methods: The neonatal patients were collected in Tianjin Children’s Hospital from January 2018 to April 2021, who had an acute illness and were suspected with genetic disorders performed by whole exome sequencing. We analysed retrospectively the clinical data, genetic findings, and the relationship between phenotype and genetic variation in this study. Results: A total of 121 neonates were enrolled in this study. Multiple organ or system were involved in the current study, mainly in metabolic, neurologic, endocrine system. The overall positive rate of whole exome sequencing was 55.4% (67/121), 94 pathogenic or likely pathogenic genomic variants of were identified in 67 neonates, of which the number of copy number varation and single-nucleotide variant were 20 and 74 respectively. The most common inheritance pattern of them was autosomal recessive, up to the rate of 56.7% (38/67), the second one was autosomal dominant inheritance, accounting for 29.8% (19/67). Up to 40 diseases were diagnosed via whole exome sequencing in this study. Conclusion: Based on the study and the available evidence of this cohort , we strongly recommend and support whole exome sequencing as the first-tier test for patients with suspected genetic disorders in neonatal intensive care unit. Whole exome sequencing demonstrates clinical utility and the significance for patients and their familes in situation of the absence of dignosis.