A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy.

Détails

ID Serval
serval:BIB_74EAE8242716
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy.
Périodique
American Journal of Human Genetics
Auteur(s)
Hor H., Bartesaghi L., Kutalik Z., Vicário J.L., de Andrés C., Pfister C., Lammers G.J., Guex N., Chrast R., Tafti M., Peraita-Adrados R.
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Statut éditorial
Publié
Date de publication
2011
Volume
89
Numéro
3
Pages
474-479
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy. Familial narcolepsy accounts for less than 10% of all narcolepsy cases. However, documented multiplex families are very rare and causative mutations have not been identified to date. To identify a causative mutation in familial narcolepsy, we performed linkage analysis in the largest ever reported family, which has 12 affected members, and sequenced coding regions of the genome (exome sequencing) of three affected members with narcolepsy and cataplexy. We successfully mapped a candidate locus on chromosomal region 6p22.1 (LOD score ¼ 3.85) by linkage analysis. Exome sequencing identified a missense mutation in the second exon of MOG within the linkage region. A c.398C>G mutation was present in all affected family members but absent in unaffected members and 775 unrelated control subjects. Transient expression of mutant myelin oligodendrocyte glycoprotein (MOG) in mouse oligodendrocytes showed abnormal subcellular localization, suggesting an altered function of the mutant MOG. MOG has recently been linked to various neuropsychiatric disorders and is considered as a key autoantigen in multiple sclerosis and in its animal model, experimental autoimmune encephalitis. Our finding of a pathogenic MOG mutation highlights a major role for myelin and oligodendrocytes in narcolepsy and further emphasizes glial involvement in neurodegeneration and neurobehavioral disorders. [corrected].
Mots-clé
Animals, Base Sequence, Cell Line, Chromosomes, Human, Pair 6/genetics, Genes, Dominant/genetics, Genetic Linkage, Genetic Predisposition to Disease/genetics, Genotype, Humans, Lod Score, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Missense/genetics, Myelin Proteins/chemistry, Myelin Proteins/genetics, Myelin-Oligodendrocyte Glycoprotein, Narcolepsy/genetics, Pedigree, Polymorphism, Single Nucleotide/genetics, Sequence Analysis, DNA, Spain
Pubmed
Web of science
Création de la notice
13/10/2011 11:36
Dernière modification de la notice
03/03/2018 18:22
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