https://www.ncbi.nlm.nih.gov/pubmed/31450232 cholestasis
Pediatr Res. 2019 Aug 26. doi: 10.1038/s41390-019-0548-8. [Epub ahead of print]
Molecular findings in children with inherited intrahepatic cholestasis.
Wang NL1, Lu Y1, Gong JY2, Xie XB1, Lin J3, Abuduxikuer K1, Zhang MH2, Wang JS4.

Abstract

BACKGROUND:
Genetic defects account for a substantial proportion of pediatric cholestasis. This study explored the molecular findings in a large cohort of Chinese patients with inherited cholestasis.

METHODS:
Between January 2012 and June 2016, 809 Chinese pediatric patients with suspected inherited intrahepatic cholestasis were evaluated by Sanger sequencing and/or panel sequencing.

RESULTS:
Of the 809 patients, 273 (33.7%) obtained a genetic diagnosis. The rate of positive genetic diagnosis in patients with disease onset at 0-3 month of age was higher than that in patients with disease onset at 4 month of age or later. There were 17 distinct genetic defects diagnosed. The top 4 resulted from mutations in SLC25A13 (44.3%), JAG1 (24.5%), ABCB11 (11.0%), and ATP8B1 (5.9%). All 17 genetic disorders were diagnosed in patients with disease onset at 0-3 months of age; but only 5 were diagnosed in patients with disease onset beyond 4 months of age. A total of 217 distinct pathogenic variants, including 41 novel variants, were identified. Ten recurrent mutations were detected in SLC25A13, ATP8B1, and CYP27A1. They accounted for 48.2% of the total 477 mutant alleles.

CONCLUSIONS:
There were 17 distinct genetic disorders diagnosed in Chinese pediatric patients with inherited cholestasis.