Biallelic mutations in ABCB1 display recurrent reversible encephalopathy

Ann Clin Transl Neurol. 2020 Aug;7(8):1443-1449. doi: 10.1002/acn3.51125. Epub 2020 Jul 5.


The clinical phenotype linked with mutations in ABCB1, encoding P-glycoprotein, has never been reported. Here, we describe twin sisters with biallelic mutations in ABCB1 who showed recurrent reversible encephalopathy accompanied by acute febrile or afebrile illness. Whole-exome sequencing was performed on one of the twin and her healthy parents, and revealed compound heterozygous loss-of-function variants in ABCB1. The patient brains displayed substantial loss of xenobiotic clearance ability, as demonstrated by [11 C]verapamil positron emission tomography (PET) study, linking this phenotype with ABCB1 function. The endogenous cytokine clearance from the brain was also decreased in LPS-treated ABCB1 knockout mice compared to controls. The results provide insights into the physiological requirement of ABCB1 in maintaining homeostasis of various compounds for normal brain function.

Publication types

  • Research Support, Non-U.S. Gov't

Grant support

This work was funded by National Research Foundation grants 2014M3C9A2064686 and 2018M3C9A5064708; Korea Centers for Disease Control and Prevention grant 2018ER690101.