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.
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Acknowledgements
Great thanks to Prof. L.-Z. Wang for the revision of the manuscript. This work was supported by the National Natural Science Foundation of China, grant numbers 81361128006 and 81570468.
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Study design: N.L.W., J.L., J.Y.G., J.S.W.; sample and data acquisition: all authors; data interpretation: Y.L., J.Y.G., X.B.X., M.H.Z.; draft manuscript: N.L.W.; statistics: N.L.W., K.A.; review and approve manuscript: all authors; accountability for work: all authors.
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Wang, NL., Lu, Y., Gong, JY. et al. Molecular findings in children with inherited intrahepatic cholestasis. Pediatr Res 87, 112–117 (2020). https://doi.org/10.1038/s41390-019-0548-8
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DOI: https://doi.org/10.1038/s41390-019-0548-8
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