Whole-exome sequencing illuminates unexplained pediatric cholestatic liver disease

Table 1 Diagnostic yield of genetic testing in pediatric liver disease from selected studies

Ref.	Population and method	Diagnostic yield	Key findings
Chen et al[7], 2025, China	80 children with unexplained liver disease; WES	57.50%	19 genes identified; 13 novel variants; WES guided therapy
Fang et al[2], 2021, China	172 children (cholestasis, elevated enzymes, hepatomegaly); WES or 62-gene panel	55.8% overall	25 genes identified; 46 novel mutations; highest yield (84.6%) in those with hepatosplenomegaly
Karpen et al[8], 2021, United States	2171 infants/children with cholestasis; 66-gene panel	12%	Top genetic diagnoses: Alagille syndrome (JAG1/NOTCH2), bile salt export pump deficiency (ABCB11), alpha-1 antitrypsin deficiency, MDR3 deficiency (ABCB4), POLG mitochondrial hepatopathy
Gürcan Kaya et al[4], 2025, Türkiye	378 neonates with cholestasis (1997-2024); targeted panel ± WES	28.00%	Genetic diagnoses increased from 18.2% before 2010 to 35.5% after 2010; common genes: ATP8B1, ABCB11, ABCB4, DCDC2, etc.
Togawa et al[9], 2016, Japan	109 infants with neonatal intrahepatic cholestasis; 18-gene panel	26% overall	71% yield in those with suspected genetic cholestasis; common diagnoses: Alagille syndrome, neonatal Dubin-Johnson syndrome, citrin deficiency, PFIC (low GGT types)
Ito et al[18], 2022, Japan	124 infants with cholestasis; expanded 61-gene panel (prospective)	26.60%	Top diagnoses: Alagille syndrome (JAG1/NOTCH2), neonatal Dubin-Johnson syndrome (ABCC2), neonatal citrin deficiency (SLC25A13) – together 78.8% of genetic cholestasis cases in Japan

WES: Whole-exome sequencing.