Biallelic mutations in ABCB1 display recurrent reversible encephalopathy

Abstract

Abstract 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 [11C]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.