NDLI: Mutations in ABHD12 Cause the Neurodegenerative Disease PHARC: An Inborn Error of Endocannabinoid Metabolism

Content Provider	PubMed Central
Author	Fiskerstrand, Torunn Brahim, Dorra H'mida-ben Johansson, Stefan Abderrahim, M'zahem Haukanes, Bjørn Ivar Drouot, Nathalie Zimmermann, Julian Cole, Andrew J. Christian, Vedeler Cecilie, Bredrup Assoum, Mirna Meriem, Tazir Klockgether, Thomas Hamri, Abdelmadjid Steen, Vidar M. Boman, Helge Bindoff, Laurence A. Koenig, Michel Knappskog, Per M.
Copyright Year	2010
Abstract	Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a neurodegenerative disease marked by early-onset cataract and hearing loss, retinitis pigmentosa, and involvement of both the central and peripheral nervous systems, including demyelinating sensorimotor polyneuropathy and cerebellar ataxia. Previously, we mapped this Refsum-like disorder to a 16 Mb region on chromosome 20. Here we report that mutations in the ABHD12 gene cause PHARC disease and we describe the clinical manifestations in a total of 19 patients from four different countries. The ABHD12 enzyme was recently shown to hydrolyze 2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that acts on cannabinoid receptors CB1 and CB2. Our data therefore represent an example of an inherited disorder related to endocannabinoid metabolism. The endocannabinoid system is involved in a wide range of physiological processes including neurotransmission, mood, appetite, pain appreciation, addiction behavior, and inflammation, and several potential drugs targeting these pathways are in development for clinical applications. Our findings show that ABHD12 performs essential functions in both the central and peripheral nervous systems and the eye. Any future drug-mediated interference with this enzyme should consider the potential risk of long-term adverse effects.
Related Links	http://dx.doi.org/10.1016/j.ajhg.2010.08.002
Ending Page	417
Page Count	8
Starting Page	410
File Format	PDF
ISSN	00029297
e-ISSN	15376605
Journal	American Journal of Human Genetics
Issue Number	3
Volume Number	87
Language	English
Publisher	Elsevier
Publisher Date	2010-09-01
Access Restriction	Open
Rights Holder	Elsevier
Subject Keyword	Genetics(clinical) Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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