Whole-exome sequencing illuminates unexplained pediatric cholestatic liver disease

Core Tip

Core Tip: The advent of whole-exome sequencing (WES) has transformed diagnosis of unexplained pediatric liver disease. In infants with cholestasis and children with cryptogenic hepatitis, comprehensive genomic testing markedly increases diagnostic yield, often exceeding 50% in recent cohorts, enabling earlier identification and management. Incorporating WES early can spare patients invasive procedures, including diagnostic liver biopsy, and facilitate timely, targeted interventions. Yet, given phenotypic heterogeneity, WES must be integrated with careful clinical assessment, family history, and selective traditional diagnostics. Falling costs and faster turnaround make WES a practical cornerstone of precision hepatology, while validation and multi-omics remain essential to realize its full potential.