Document Detail


Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2.
MedLine Citation:
PMID:  12539047     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Headache attacks and autonomic dysfunctions characterize migraine, a very common, disabling disorder with a prevalence of 12% in the general population of Western countries. About 20% of individuals affected with migraine experience aura, a visual or sensory-motor neurological dysfunction that usually precedes or accompanies the headache. Although the mode of transmission is controversial, population-based and twin studies have implicated genetic factors, especially in migraine with aura. Familial hemiplegic migraine is a hereditary form of migraine characterized by aura and some hemiparesis. Here we show that mutations in the gene ATP1A2 that encodes the alpha2 subunit of the Na+/K+ pump are associated with familial hemiplegic migraine type 2 (FHM2) linked to chromosome 1q23 (OMIM 602481). Functional data indicate that the putative pathogenetic mechanism is triggered by a loss of function of a single allele of ATP1A2. This is the first report associating mutations of Na+K+ pump subunits to genetic diseases.
Authors:
Maurizio De Fusco; Roberto Marconi; Laura Silvestri; Luigia Atorino; Luca Rampoldi; Letterio Morgante; Andrea Ballabio; Paolo Aridon; Giorgio Casari
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-01-21
Journal Detail:
Title:  Nature genetics     Volume:  33     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-01-31     Completed Date:  2003-03-04     Revised Date:  2012-02-22    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  192-6     Citation Subset:  IM    
Affiliation:
Human Molecular Genetics Unit, Dibit-San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
Data Bank Information
Bank Name/Acc. No.:
OMIM/141500;  602481; RefSeq/NM_001678
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
COS Cells
Calcium Channels / genetics
Case-Control Studies
Cell Survival / drug effects
Cercopithecus aethiops
Chromatography, High Pressure Liquid
Chromosomes, Human, Pair 1 / genetics
Drug Resistance
Enzyme Inhibitors / pharmacology
Female
Haploidy
HeLa Cells
Humans
Male
Migraine with Aura / enzymology*,  genetics*
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation*
Ouabain / pharmacology
Pedigree
Peptide Fragments
Sodium-Potassium-Exchanging ATPase / genetics*,  metabolism
Transfection
Grant Support
ID/Acronym/Agency:
F.1//Telethon; TGM06S01//Telethon
Chemical
Reg. No./Substance:
0/Calcium Channels; 0/Enzyme Inhibitors; 0/Peptide Fragments; 630-60-4/Ouabain; EC 3.6.1.-/ATP1A2 protein, human; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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