Next-generation sequencing is a useful tool for the diagnosis of cholestasis in children, according to a new study published in Diagnostics. The approach was able to diagnose almost a third (28.1%) of the patients included in the study.

“In the remaining patients, especially those with variants of uncertain significance, the imputability of the variants requires further investigations,” the authors of the study wrote. Cholestasis is common during childhood with a quarter of cases being genetic for example due to Alagille syndrome (ALGS).

Researchers have proposed that molecular analysis by targeted-capture next-generation sequencing could be an efficient diagnostic tool for cholestasis in children. In the present study, a team led by Emmanuel Gonzales, MD, PhD, evaluated the effectiveness of next-generation sequencing in children with the condition.

Continue Reading

A total of 602 children with cholestasis were analyzed by targeted capture of a panel of 34 genes, which are known to play a role in cholestasis and jaundice.

Read more about the etiology of ALGS

Of these 602 children, 169 were classified as “certain diagnosis.” Of the remaining 433 patients, 40 were classified as “suggested diagnosis” where the genotype was consistent with phenotype for disease without any Online Mendelian Inheritance in Man or OrphaNet-number, and 21 were classified as “uncertain diagnosis” where clinical and paraclinical findings were not consistent with molecular findings. The approach did not identify any molecular defects in the remaining 372 children.

“For some patients, the interpretation of molecular findings should be considered an ongoing process, which deserves to be updated taking into account newly published data and the clinical evolution of the patients,” the authors said.

In ALGS, bile duct paucity leads to chronic cholestasis, jaundice, and hyperbilirubinemia depending on severity. The disease is caused by a mutation in the JAG1 gene in the majority of cases.


Almes M, Spraul A, Ruiz M, et al. Targeted-capture next-generation sequencing in diagnosis approach of pediatric cholestasis. Diagnostics. 2022;12(5):1169. doi:10.3390/diagnostics12051169