Kleine-Levin syndrome is associated with LMOD3 variants.

Details

Serval ID
serval:BIB_193D58CD77E1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Kleine-Levin syndrome is associated with LMOD3 variants.
Journal
Journal of sleep research
Author(s)
Al Shareef S.M., Basit S., Li S., Pfister C., Pradervand S., Lecendreux M., Mayer G., Dauvilliers Y., Salpietro V., Houlden H., BaHammam A.S., Tafti M.
ISSN
1365-2869 (Electronic)
ISSN-L
0962-1105
Publication state
Published
Issued date
06/2019
Peer-reviewed
Oui
Volume
28
Number
3
Pages
e12718
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Kleine-Levin syndrome (KLS) is a rare periodic hypersomnia with associated behavioural abnormalities but with often favourable prognosis. There is excess risk of KLS in first-degree relatives, suggesting a strong genetic contribution. So far, no mutation is identified in KLS and comprehensive genetic analysis of affected individuals is lacking. Here we performed whole genome single-nucleotide polymorphism (SNP) genotyping and exome sequencing in a large family with seven affected members. The identified gene with a mutation was resequenced in 38 sporadic KLS patients and the expression of the gene product was mapped in the mouse brain. Linkage analysis mapped the disease locus to chromosome 3 and exome analysis identified a heterozygous missense variant in LMOD3 (p.E142D) in the linkage interval. The variant was found to segregate in all affected and one presumably unaffected member of the family. Resequencing LMOD3 in 38 other KLS patients and their families revealed three other low frequency or rare missense variants in seven cases that were inherited with incomplete penetrance. LMOD3 is expressed in the brain and colocalized with major structures involved in the regulation of vigilance states. LMOD proteins are structural proteins and seem to be developmentally regulated. Our findings suggest that KLS might be a structural/neurodevelopmental brain disease.
Keywords
Adolescent, Adult, Animals, Brain/metabolism, Female, Humans, Kleine-Levin Syndrome/genetics, Kleine-Levin Syndrome/metabolism, Male, Mice, Microfilament Proteins/biosynthesis, Microfilament Proteins/genetics, Microfilament Proteins/metabolism, Nervous System Diseases/genetics, Nervous System Diseases/metabolism, Polymorphism, Single Nucleotide, Young Adult, Leiomodin 3, exome, hypocretin, lateral hypothalamus, linkage, periodic hypersomnia
Pubmed
Web of science
Create date
16/07/2018 16:49
Last modification date
05/04/2020 5:20
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