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| Status |
Public on Aug 27, 2010 |
| Title |
Mutations in ABHD12 cause the neurodegenerative disease PHARC: An inborn error of endocannabinoid metabolism |
| Organism |
Homo sapiens |
| Experiment type |
SNP genotyping by SNP array
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| Summary |
PHARC is a neurodegenerative disease comprising 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 hydrolyse 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 behaviour 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.
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| Overall design |
Homozygosity mapping using Affymetrix 250K SNP arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples. This accession number contains the data for families 1-5 plus 7 in the article.
Supplementary files linked below.
The region of interest on chromosome 20 was found using families 1 and 2. The patients in families 3,4 and 5 were then recruited and the patients were homozygous for the same region on chromosome 20 as those in families 1 and 2, showing that all these patients are distantly related. All affected are homozygous for the same mutation. The rest of the chromosomes fall outside the scope of our study.
Mutations in ABHD12 Cause the Neurodegenerative Disease PHARC: An Inborn Error of Endocannabinoid Metabolism, Fiskerstrand et al. The American Journal of Human Genetics, 26 August 2010
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B8JDD-50W2K9M-3&_user=6129429&_coverDate=08%2F26%2F2010&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000000150&_version=1&_urlVersion=0&_userid=6129429&md5=234296648f66debd3e2b08e795f2179f
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| Contributor(s) |
Fiskerstrand T |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jul 26, 2010 |
| Last update date |
May 17, 2017 |
| Contact name |
Torunn Fiskerstrand |
| E-mail(s) |
torunn.fiskerstrand@netcom.no, torunn.fiskerstrand@helse-bergen.no
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| Phone |
+4755975481
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| Fax |
+4755975479
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| Organization name |
Haukeland University Hospital
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| Department |
Center for medical genetics and molecular medicine
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| Street address |
Jonas Lies vei
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| City |
Bergen |
| ZIP/Postal code |
5021 |
| Country |
Norway |
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| Platforms (1) |
| GPL3718 |
[Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array |
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| Samples (26)
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| GSM587967 |
Family 1, affected individual 1.1 (30907) |
| GSM587968 |
Family 1, affected individual 1.2 (31264) |
| GSM587969 |
Family 1, affected individual 1.3 (30906) |
| GSM587970 |
Family 1, mother of 1.1 and 1.2 (30936) |
| GSM587971 |
Family 1, father of 1.1 and 1.2 (30935) |
| GSM587972 |
Family 1, healthy brother of 1.1 and 1.2 (30937) |
| GSM587973 |
Family 1, mother of 1.3 (30825) |
| GSM587974 |
Family 1, father of 1.3 (30824) |
| GSM587975 |
Family 1, healthy sister of 1.3 (31098) |
| GSM587976 |
Family 1, healthy sister of 1.3 (30924) |
| GSM587977 |
Family 1, healthy sister of 1.3 (30832) |
| GSM587978 |
Family 2, affected individual 2.1 (61188) |
| GSM587979 |
Family 2, affected individual 2.2 (83591) |
| GSM587980 |
Family 2, healthy brother of 2.1 and 2.2 (83843) |
| GSM587981 |
Family 2, healthy brother of 2.1 and 2.2 (83592) |
| GSM587982 |
Family 2, healthy sister of 2.1 and 2.2 (90084) |
| GSM587983 |
Family 3, affected individual 3.1 (51589) |
| GSM587984 |
Family 3, mother of 3.1 (92047) |
| GSM587985 |
Family 3, father of 3.1 (92146) |
| GSM587986 |
Family 4, affected individual 4.1 (70532) |
| GSM587987 |
Family 4, mother of 4.1 (91923) |
| GSM587988 |
Family 4, father of 4.1 (92227) |
| GSM587989 |
Family 5, affected individual 5.1 (92321) |
| GSM587990 |
Family 5, mother of 5.1 (92931) |
| GSM587991 |
Family 5, father of 5.1 (92930) |
| GSM587992 |
Family 7, affected individual 7.1 (91999) |
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| Relations |
| BioProject |
PRJNA131569 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23151_Family1_genotypecalls_sorted.txt.gz |
719.5 Kb |
(ftp)(http) |
TXT |
| GSE23151_Family1_genotypecalls_sorted.xml.gz |
1.1 Mb |
(ftp)(http) |
XML |
| GSE23151_Family2_genotypecalls_sorted.txt.gz |
621.0 Kb |
(ftp)(http) |
TXT |
| GSE23151_Family2_genotypecalls_sorted.xml.gz |
906.1 Kb |
(ftp)(http) |
XML |
| GSE23151_Family3_genotypecalls_chromosome20_sorted.txt.gz |
74.8 Kb |
(ftp)(http) |
TXT |
| GSE23151_Family3_genotypecalls_chromosome20_sorted.xml.gz |
106.8 Kb |
(ftp)(http) |
XML |
| GSE23151_Family4_genotypecalls_chromosome20_sorted.txt.gz |
74.2 Kb |
(ftp)(http) |
TXT |
| GSE23151_Family4_genotypecalls_chromosome20_sorted.xml.gz |
105.6 Kb |
(ftp)(http) |
XML |
| GSE23151_Family5_genotypecalls_chromosome20_sorted.txt.gz |
73.7 Kb |
(ftp)(http) |
TXT |
| GSE23151_Family5_genotypecalls_chromosome20_sorted.xml.gz |
105.1 Kb |
(ftp)(http) |
XML |
| GSE23151_Family7_genotypecalls_sorted.txt.gz |
578.6 Kb |
(ftp)(http) |
TXT |
| GSE23151_Family7_genotypecalls_sorted.xml.gz |
785.1 Kb |
(ftp)(http) |
XML |
| GSE23151_RAW.tar |
745.1 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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