Biallelic mutations in ABCB1 display recurrent reversible encephalopathy

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 w...

Full description

Bibliographic Details
Main Authors:	Jieun Seo, Cho‐Rong Lee, Jin Chul Paeng, Hyun W. Kwon, Duckgue Lee, Soon‐Chan Kim, Jaeseok Han, Ja‐Lok Ku, Jong Hee Chae, Byung Chan Lim, Murim Choi
Format:	Article
Language:	English
Published:	Wiley 2020-08-01
Series:	Annals of Clinical and Translational Neurology
Online Access:	https://doi.org/10.1002/acn3.51125

id	doaj-bfcd5c10bf4c43c1a7cf9258d3054069
record_format	Article
spelling	doaj-bfcd5c10bf4c43c1a7cf9258d30540692021-05-02T23:51:09ZengWileyAnnals of Clinical and Translational Neurology2328-95032020-08-01781443144910.1002/acn3.51125Biallelic mutations in ABCB1 display recurrent reversible encephalopathyJieun Seo0Cho‐Rong Lee1Jin Chul Paeng2Hyun W. Kwon3Duckgue Lee4Soon‐Chan Kim5Jaeseok Han6Ja‐Lok Ku7Jong Hee Chae8Byung Chan Lim9Murim Choi10Department of Biomedical Sciences Seoul National University College of Medicine Seoul Republic of KoreaDepartment of Biomedical Sciences Seoul National University College of Medicine Seoul Republic of KoreaDepartment of Nuclear Medicine Seoul National University College of Medicine Seoul Republic of KoreaDepartment of Nuclear Medicine Korea University Anam Hospital Seoul Republic of KoreaSoonchunhyang Institute of Medi‐Bio Science Soonchunhyang University Cheonan Republic of KoreaDepartment of Biomedical Sciences Seoul National University College of Medicine Seoul Republic of KoreaSoonchunhyang Institute of Medi‐Bio Science Soonchunhyang University Cheonan Republic of KoreaDepartment of Biomedical Sciences Seoul National University College of Medicine Seoul Republic of KoreaDepartment of Pediatrics Seoul National University College of Medicine Seoul Republic of KoreaDepartment of Pediatrics Seoul National University College of Medicine Seoul Republic of KoreaDepartment of Biomedical Sciences Seoul National University College of Medicine Seoul Republic of KoreaAbstract 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.https://doi.org/10.1002/acn3.51125
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Jieun Seo Cho‐Rong Lee Jin Chul Paeng Hyun W. Kwon Duckgue Lee Soon‐Chan Kim Jaeseok Han Ja‐Lok Ku Jong Hee Chae Byung Chan Lim Murim Choi
spellingShingle	Jieun Seo Cho‐Rong Lee Jin Chul Paeng Hyun W. Kwon Duckgue Lee Soon‐Chan Kim Jaeseok Han Ja‐Lok Ku Jong Hee Chae Byung Chan Lim Murim Choi Biallelic mutations in ABCB1 display recurrent reversible encephalopathy Annals of Clinical and Translational Neurology
author_facet	Jieun Seo Cho‐Rong Lee Jin Chul Paeng Hyun W. Kwon Duckgue Lee Soon‐Chan Kim Jaeseok Han Ja‐Lok Ku Jong Hee Chae Byung Chan Lim Murim Choi
author_sort	Jieun Seo
title	Biallelic mutations in ABCB1 display recurrent reversible encephalopathy
title_short	Biallelic mutations in ABCB1 display recurrent reversible encephalopathy
title_full	Biallelic mutations in ABCB1 display recurrent reversible encephalopathy
title_fullStr	Biallelic mutations in ABCB1 display recurrent reversible encephalopathy
title_full_unstemmed	Biallelic mutations in ABCB1 display recurrent reversible encephalopathy
title_sort	biallelic mutations in abcb1 display recurrent reversible encephalopathy
publisher	Wiley
series	Annals of Clinical and Translational Neurology
issn	2328-9503
publishDate	2020-08-01
description	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.
url	https://doi.org/10.1002/acn3.51125
work_keys_str_mv	AT jieunseo biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy AT choronglee biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy AT jinchulpaeng biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy AT hyunwkwon biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy AT duckguelee biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy AT soonchankim biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy AT jaeseokhan biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy AT jalokku biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy AT jongheechae biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy AT byungchanlim biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy AT murimchoi biallelicmutationsinabcb1displayrecurrentreversibleencephalopathy
_version_	1721486551331897344

Biallelic mutations in ABCB1 display recurrent reversible encephalopathy

Similar Items